Lasso filter tipped microcatheter for simultaneous rotating separator, irrigator for thrombectomy and method for use

ABSTRACT

The invention provides a filter assembly including a string or wire such that a lasso type cincture is effected, said filter being openable and closeable while in deployed within a bodily vessel. A string lengthen or shorting adjustment mechanism, such as a ratchet or reel allows more length of string into the device or alternatively to shorten the length of available string in the system. The described invention, when used to ameliorate venous clots and most arterio-venous dialysis grafts, a filter-tipped aspirator is used downstream from the clot to capture and remove dislocated emboli. A method of using same is disclosed.

CROSS-REFERENCE(S)

This is a continuation-in-part (C-I-P) claiming priority to C-I-Papplication Ser. No. 16/125,691, filed Sep. 8, 2018 (8 Sep. 2018), whichin turn claims priority to C-I-P application Ser. No. 15/731,478 filedJun. 16, 2017 (16 Jun. 2017), which claims priority to C-I-P applicationSer. No. 15/530,898 filed Mar. 20, 2017 (20 Mar. 2017), which claimspriority to nonprovisional application Ser. No. 15/258,877 filed Sep. 7,2016 (7 Sep. 2016); each of which is incorporated by reference.

FIELD OF THE INVENTION

The present invention provides a medical device for use in vascularprocedures. The device employs the simultaneous application ofirrigating, aspirating and macerating for the purpose of safely andeffectively performing thrombectomy or the like. More particularly, thepresent invention discloses a “string length adjustment mechanism” for alasso, namely a mechanism to allow more lengths of string into “system”,or alternatively to shorten the length of available string in thesystem, namely a ratchet, or a reel among others. Said system is part ofa filter assembly that is openable and closeable while in use within abodily vessel, by deployment of a string or wire arranged such that alasso or drawstring type cincture is effected.

BACKGROUND OF THE INVENTION Prior Art

Prior art is replete with documentation as the direct and indirectadverse health effects associated with the presence of solid matterwithin an individual's vascular system. One common example of saidmatter is a thrombus. A wide variety of techniques are known forremoving said mater from a vascular system. Said techniques often use,independently, both electrical and mechanical thrombus macerationdevices, irrigation devices or aspiration devices. Typically, saidtechniques attempt to dislodge said solid matter from the contours ofthe vascular system, if necessary, and then remove said solid matterfrom the vascular system by means of suction or the like or retrievaldevices.

For purposes of thrombectomy some skilled persons (usually doctors) useone or more tools such as mechanical thrombus maceration devices,irrigation devices, clot retrieval devices and aspiration devices.

The application of irrigation alone into the clot would tend topropagate any loose pieces—whether they are existing loose pieces orlose pieces created by maceration. In Arterial clots in particular theirrigation alone would tend to propagate the loose pieces distally intothe smaller arteries and capillary beds. Once they get that far distal,they will clog the capillary beds, cannot be retrieved, and will causepermanent ischemic injury to the tissues. By applying simultaneousproximal aspiration, while occluding the vessel with a wedged occlusivesize catheter with or without a catheter with a balloon inflated on thetip, flow at the clot and the artery beyond will be reversed, and loosepieces will flow retrograde into the aspiration catheter and out of thebody, rather than traveling downstream and making matters worse. Withthe flow reversed for safety the irrigation will prevent an empty vacuumwhere nothing will flow, and will prevent collapse of the artery fromthe vacuum that also would not allow flow.

In venous clots the same principles apply. Specifically, that the usermust to prevent the showering of loose pieces of clot (emboli) to thecapillary beds of the at-risk tissue, but the at-risk tissue isdifferent—based on the direction of flow. In venous clots the at-risktissue is in the heart and lungs—as the venous flow takes the blood backto the right side of the heart and then the lungs. So, in venous casesthe key is to pick up the clot pieces before they hit the heart orlungs. Venous cases have a further disadvantage that the vessels withthrombus are typically much larger, so if continuous simultaneousaspiration was applied, the patient would have massive blood loss. Onthe other hand, venous cases have the advantage, in most cases, thatthey can be approached easily from either side of the clot—from belowand above (further from the heart and closer to the heart). For example(non-limiting)—an iliac clot can be approached with an irrigatingmacerator, or a plain macerator, from below via the femoral vein. Anovel filter aspirator described by the current invention can then beintroduced into the internal jugular vein in the neck, advanced over awire down through the right atrium of the heart and deployed in theinferior vena cava, above the clot—so all showered pieces end up in thefilter, and not in the capillary beds of the heart and lungs (smallpieces) or in the main pulmonary arteries (larger pieces)—which cancause life threatening hemodynamic instability (a classic largepulmonary embolus). The aspiration on the filter aspirator would only beturned on intermittently, to clear out the clot accumulating at thefilter, so as to avoid the massive blood loss that would otherwise occurif the aspiration was on continuously in these cases. In an alternativesetup the macerating tool could also be introduced through the filteraspirator. A similar application of this novel filter aspirator could beused to capture and remove emboli during a “declot” procedure for anobstructed dialysis arterio venous graft fistula. In this case thefilter aspirator would more often be introduced via the femoral vein,and deployed in the axillary vein or the Subclavian vein. This is incontrast to the arterial example above—where blood flow to that arterialterritory is intentionally occluded—so very little blood isaspirated—mostly clot and irrigation. Furthermore, in most arterialapplications, even when there is back bleeding from collateral flow, thevessels are typically much smaller so flow rate of blood that can belost is much lower.

In venous thrombectomy cases the described technique is currently notdone because a filter aspirator does not exist. Additionally,

If it did exist and aspiration was applied continuously, in many ofthese cases there could be massive, often life-threatening, blood loss.

In arterial thrombectomy cases irrigation is not used with theaspiration because in smaller arteries there is a technical/engineeringchallenges of making a device small enough to effectively irrigatethrough and macerate, while not functionally obstructing the aspirationcatheter (if the device fills too much of the aspiration catheter, theeffective diameter of the aspiration catheter is reduced tremendously.Flow is inversely proportional to the fourth power of diameter

$R = \frac{8\mspace{14mu} L\mspace{14mu}\eta}{\pi\mspace{14mu} r^{4}}$

where r=inside radius of the vessel, L=vessel length, and η=bloodviscosity.

It is important to note that a small change in vessel radius will have avery large influence (4th power) on its resistance to flow; e.g.,decreasing vessel diameter by 50% will increase its resistance to flowby approximately 16-fold.

More particularly, if one combines the preceding two equations into oneexpression, which is commonly known as the Poiseuille equation, it canbe used to better approximate the factors that influence flow through acylindrical vessel:

$Q = \frac{\Delta\; P\mspace{14mu}\pi\mspace{14mu} r^{4}}{8\mspace{14mu} L\mspace{14mu}\eta}$

Aspiration may lead to the collapse of a blood vessel.

Additionally, the art would lead a skilled person away from the presentinvention's simultaneous combination because the simultaneous use of anirrigation device and aspiration device are counter synergistic (i.e.they would cancel out each other's intended benefit). Consequently, theprior art teaches the use of the serial use of an irrigation device andthen an aspiration device.

Accordingly, it would be desirable to provide a means of applying asimultaneous combination of irrigation, aspiration and maceration to athrombus or similar material.

Blood Vessel Structure and Function

Blood vessels are dynamic structures that constrict, relax, pulsate, andproliferate. Within the body, blood vessels form a closed deliverysystem that begins and ends at the heart. There are three major types ofblood vessels: (i) arteries; (ii) capillaries and (iii) veins. As theheart contracts, it forces blood into the large arteries leaving theventricles. Blood then moves into smaller arteries successively, untilfinally reaching the smallest branches, the arterioles, which feed intothe capillary beds of organs and tissues. Blood drains from thecapillaries into venules, the smallest veins, and then into larger veinsthat merge and ultimately empty into the heart.

Arteries carry blood away from the heart and “branch” as they formsmaller and smaller divisions. In contrast, veins carry blood toward theheart and “merge” into larger and larger vessels approaching the heart.In the systemic circulation, arteries carry oxygenated blood and veinscarry oxygen-poor blood. In the pulmonary circulation, the opposite istrue. The arteries (still defined as the vessels leading away from theheart), carry oxygen-poor blood to the lungs, and the veins carryoxygen-rich blood from the lungs to the heart.

The only blood vessels that have intimate contact with tissue cells inthe human body are capillaries. In this way, capillaries help servecellular needs. Exchanges between the blood and tissue cells occurprimarily through the thin capillary walls.

The walls of most blood vessels (the exception being the smallestvessels, e.g., venules), have three layers, or tunics, that surround acentral blood-containing space called the vessel lumen.

The innermost tunic (layer) is the tunica intima. The tunica intimacontains the endothelium, the simple squamous epithelium that lines thelumen of all vessels. The endothelium is continuous with the endocardiallining of the heart, and its flat cells fit closely together, forming aslippery surface that minimizes friction so blood moves smoothly throughthe lumen. In vessels larger than 1 mm in diameter, a sub-endotheliallayer, consisting of a basement membrane and loose connective tissue,supports the endothelium.

The middle tunic (layer), the tunica media, is mostly circularlyarranged smooth muscle cells and sheets of elastin. The activity of thesmooth muscle is regulated by sympathetic vasomotor nerve fibers of theautonomic nervous system. Depending on the body's needs at any giventime, regulation causes either vasoconstriction (lumen diameterdecreases) or vasodilation (lumen diameter increases). The activities ofthe tunica media are critical in regulating the circulatory systembecause small changes in vessel diameter greatly influence blood flowand blood pressure. Generally, the tunica media is the bulkiest layer inarteries, which bear the chief responsibility for maintaining bloodpressure and proper circulation.

The outer layer of a blood vessel wall, the tunica externa, is primarilycomposed of collagen fibers that protect the vessel, reinforce thevessel, and anchor the vessel to surrounding structures. The tunicaexterna contains nerve fibers, lymphatic vessels, and elastic fibers(e.g., in large veins). In large vessels, the tunica externa contains astructure known as the vasa vasorum, which literally means “vessels ofvessels”. The vasa vasorum nourishes external tissues of the bloodvessel wall. Interior layers of blood vessels receive nutrients directlyfrom blood in the lumen (See, e.g., The Cardiovascular System at aGlance, 4th Edition, Philip I. Aaronson, Jeremy P. T. Ward, Michelle J.Connolly, November 2012, 2012, Wiley-Blackwell, Hoboken, N.J.).

Cerebral Arteries

FIGS. 1 and 2 show schematic illustrations of the brain's blood vessels.Each cerebral hemisphere is supplied by an internal carotid artery,which arises from a common carotid artery beneath the angle of the jaw,enters the cranium through the carotid foramen, traverses the cavernosussinus (giving off the ophthalmic artery), penetrates the dura anddivides into the anterior and middle cerebral arteries. The largesurface branches of the anterior cerebral artery supply the cortex andwhite matter of the inferior frontal lobe, the medial surface of thefrontal and parietal lobes and the anterior corpus callosum. Smallerpenetrating branches supply the deeper cerebrum and diencephalon,including limbic structures, the head of the caudate, and the anteriorlimb of the internal capsule. The large surface branches of the middlecerebral artery supply most of the cortex and white matter of thehemisphere's convexity, including the frontal, parietal, temporal andoccipital lobes, and the insula. Smaller penetrating branches supply thedeep white matter and diencephalic structures such as the posterior limbof the internal capsule, the putamen, the outer globus pallidus, and thebody of the caudate. After the internal carotid artery emerges from thecavernous sinus, it also gives off the anterior choroidal artery, whichsupplies the anterior hippocampus and, at a caudal level, the posteriorlimb of the internal capsule. Each vertebral artery arises from asubclavian artery, enters the cranium through the foramen magnum, andgives off an anterior spinal artery and a posterior inferior cerebellarartery. The vertebral arteries join at the junction of the pons and themedulla to form the basilar artery, which at the level of the pons givesoff the anterior inferior cerebellar artery and the internal auditoryartery, and, at the midbrain, the superior cerebellar artery. Thebasilar artery then divides into the two posterior cerebral arteries.The large surface branches of the posterior cerebral arteries supply theinferior temporal and medial occipital lobes and the posterior corpuscallosum; the smaller penetrating branches of these arteries supplydiencephalic structures, including the thalamus and the subthalamicnuclei, as well as part of the midbrain (see Principles of NeuralSciences, 2d Ed., Eric R. Kandel and James H. Schwartz, Elsevier SciencePublishing Co., Inc., New York, pp. 854-56 (1985)).

Interconnections between blood vessels (anastomoses) protect the brainwhen part of its vascular supply is compromised. At the circle ofWillis, the two anterior cerebral arteries are connected by the anteriorcommunicating artery and the posterior cerebral arteries are connectedto the internal carotid arteries by the posterior communicatingarteries. Other important anastomoses include connections between theophthalmic artery and branches of the external carotid artery throughthe orbit, and connections at the brain surface between branches of themiddle, anterior, and posterior cerebral arteries (Principles of NeuralSciences, 2d Ed., Eric R. Kandel and James H. Schwartz, Elsevier SciencePublishing Co., Inc., New York, pp. 854-56 (1985)).

Hemorrhage

Blood vessels are typically structurally adept to withstand the dynamicquantities required to maintain circulatory function. For reasons thatare not entirely understood, the vessel wall can become fatigued andabnormally weak and possibly rupture. With vessel rupture, hemorrhage(meaning the escape of blood from a ruptured blood vessel) occurs withblood seeping into the surrounding brain tissue. As the bloodaccumulates within the brain, the displaced volume causes the blood, nowthrombosed (clotted), to ultimately compress the surrounding vessels.The compression of vessels translates into a reduced vessel diameter anda corresponding reduction in flow to surrounding tissue, therebyenlarging the insult (See, e.g., Hademenos G. J. and Massoud T. F.Stroke 1997; 28: 2067-2077).

In the brain, hemorrhage may occur at the brain surface(extraparenchymal), for example, from the rupture of congenitalaneurysms at the circle of Willis, causing subarachnoid hemorrhage(SAH). Hemorrhage also may be intraparenchymal, for example, fromrupture of vessels damaged by long-standing hypertension, and may causea blood clot (intracerebral hematoma) within the cerebral hemispheres,in the brain stem, or in the cerebellum. Hemorrhage may be accompaniedby ischemia or infarction. The mass effect of an intracerebral hematomamay compromise the blood supply of adjacent brain tissue; or SAH maycause reactive vasospasm of cerebral surface vessels, leading to furtherischemic brain damage. Infarcted tissue may also become secondarilyhemorrhagic. Among the vascular lesions that can lead to hemorrhagicstrokes are aneurysms and arteriovenous malformations (AVMs) (See, e.g.,Hademenos G. J. and Massoud T. F. Stroke 1997; 28: 2067-2077).

Coagulation

Hemostasis is the cessation of blood loss from a damaged vessel.Platelets first adhere to macromolecules in the subendothelial regionsof the injured blood vessel; they then aggregate to form a primaryhemostatic plug. Platelets stimulate local activation of plasmacoagulation factors, leading to generation of a fibrin clot thatreinforces the platelet aggregate. Later, as wound healing occurs, theplatelet aggregate and fibrin clot are degraded as wound healing, ensues(Goodman & Gilman's The Pharmacological Basis of Therapeutics, Joel G.Hardman and Lee E. Limbird, Eds, McGraw-Hill, 2001, p. 1519-20).

Coagulation involves a series of zymogen activation reactions. At eachstage, a precursor protein, or zymogen, is converted to an activeprotease by cleavage of one or more peptide bonds in the precursormolecule. The components that can be involved at each stage include aprotease from the preceding stage, a zymogen, a non-enzymatic proteincofactor, calcium ions, and an organizing surface that is provided bythe damaged blood vessel and platelets in vivo. The final protease to begenerated is thrombin (factor IIa).

Fibrinogen is a 330,000 dalton protein that consists of three pairs ofpolypeptide chains (designated α, β and γ) covalently linked bydisulfide bonds. Thrombin converts fibrinogen to fibrin monomers (FactorIA) by cleaving fibrinopeptides A (16 amino acid residues) and B (14amino acid residues) from the amino-terminal ends of the α and β chainsrespectively. Removal of the fibrinopeptides allows the fibrin monomersto form a gel. Initially, the fibrin monomers are bound to each othernon-covalently. Subsequently, factor XIIIa catalyzes an interchaintransglutamination reaction that cross-links adjacent fibrin monomers toenhance the strength of the clot.

Fibrin participates in both the activation of Factor XIII by thrombinand activation of plasminogen activator (t-PA). It specifically bindsthe activated coagulation factors factor Xa and thrombin and entrapsthem in the network of fibers, thus functioning as a temporary inhibitorof these enzymes which stay active and can be released duringfibrinolysis. Recent research comprises shown that fibrin plays a keyrole in the inflammatory response.

The protease zymogens involved in coagulation include factors II(prothrombin), VII, IX, X, XI, XII, and prekallikrein. Factors V andVIII are homologous 350,000 dalton proteins. Factor VIII circulates inplasma bound to von Willebrand factor, while factor V is present bothfree in plasma and as a component of platelets. Thrombin cleaves V andVIII to yield activated factors (Va and VIIIa) that have at least 50times the coagulant activity of the precursor forms. Factors Va andVIIIa have no enzymatic activity themselves, but serve as cofactors thatincrease the proteolytic efficiency of Xa and IXa, respectively. Tissuefactor (TF) is a non-enzymatic lipoprotein cofactor that greatlyincreases the proteolytic efficiency of VIIa. It is present on thesurface of cells that are not normally in contact with blood and plasma(e.g. fibroblasts and smooth muscle cells) since they are abluminal to(meaning on the outer surface of a body part with an internal cavity orchannel) the endothelium. TF is a key factor that initiates coagulationoutside a broken blood vessel.

Two pathways of coagulation are recognized: the intrinsic coagulationpathway, so called because all of the components are intrinsic toplasma, and an extrinsic coagulation pathway. The extrinsic andintrinsic systems converge to activate the final common pathways causingfibrin formation. FIG. 1 shows an illustrative representation of theclassic coagulation cascades. It generally is recognized that thesesystems are somewhat artificial distinctions and do not reflectaccurately the coagulation cascades that occur in vivo. Hoffman, M., andMonroe, D. M. III, ‘A Cell-based Model of Hemostasis,” Thromb. Haemost.85: 958-65 (2001). Tissue factor exposed by tissue injury, eithertraumatically, by disease or surgery, can activate sufficient factors X,IX and thrombin (II) to initiate coagulation.

The extrinsic system (tissue factor (TF) pathway) generates a thrombinburst and is initiated when tissue thromboplastin activates Factor VII.Upon vessel injury, TF is exposed to the blood and enzyme coagulationFactor VII (proconvertin) circulating in the blood. Once bound to TF,Factor VII is activated to Factor VIIa by different proteases, includingthrombin (Factor Ha), Factor Xa, Factor IXa, Factor XIIa and the FactorVIIa-TF complex itself. The Factor VIIa-TF complex activates Factors IXand X. The activation of Factor Xa by Factor VIIa-TF almost immediatelyis inhibited by tissue factor pathway inhibitor (TFPI). Factor Xa andits cofactor Va form the prothrombinase complex which activates theconversion of prothrombin to thrombin. Thrombin then activates othercomponents of the coagulation cascade, including Factor V and FactorVIII (which activates Factor XI, which, in turn, activates Factor IX),and activates and releases Factor VIII from being bound to vWF (vonWillebrand Factor). Factor VIIa and Factor IXa together they form the“tenase” complex, which activates Factor X, and so the cycle continues.

The intrinsic system (contact activation pathway) is initiated whenblood contacts any surface except normal endothelial and blood cells.The intrinsic system begins with formation of the primary complex oncollagen by high-molecular weight kininogen (HMWK), prekallikrein, andFXII (Hageman factor). Prekallikrein is converted to kallikrein andFactor XII becomes Factor XIIa. Factor XIIa converts Factor XI intoFactor XIa. Factor XIa activates Factor IX, which, with its co-factorFactor VIIIa form the tenase complex, which activates Factor X to FactorXa.

The prevailing view of hemostasis remains that the protein coagulationfactors direct and control the process with cells serving primarily toprovide a phosphatidylserine containing surface on which theprocoagulant complexes are assembled. In contrast, a model in whichcoagulation is regulated by properties of cell surfaces, whichemphasized the importance of specific cellular receptors for thecoagulation proteins, comprises been proposed. Hoffman, M., and Monroe,D. M. III, ‘A Cell-based Model of Hemostasis,” Thromb. Haemost. 85:958-65 (2001). Thus, cells with similar phosphatidylserine content canplay very different roles in hemostasis depending on their complement ofsurface receptors. These authors propose that coagulation occurs not asa “cascade”, but in three overlapping stages: 1) initiation, whichoccurs on a tissue factor bearing cell; 2) amplification, in whichplatelets and cofactors are activated to set the stage for large scalethrombin generation; and 3) propagation, in which large amounts ofthrombin are generated on the platelet surface. This cell-based modelexplains some aspects of hemostasis that a protein-centric model doesnot.

Modeling Hemostasis

As currently understood, coagulation in vivo is a 3-step processcentered on cell surfaces. FIG. 2 shows an illustration of thecell-surface based model of coagulation in vivo (Monroe ArteriosclerThromb Vasc Biol. 2002; 22:1381-1389). In the first step, coagulationbegins primarily by initiation with tissue factor (TF), which is presenton the subendothelium, tissues not normally exposed to blood, activatedmonocytes and endothelium when activated by inflammation. Factors VIIand VIIa bind to TF and adjacent collagen. The factor VIIa-tissue factorcomplex activates factor X and IX. Factor Xa activates factor V, forminga prothrombinase complex (factor Xa, Va and calcium) on theTF-expressing cell. In the second step, coagulation is amplified asplatelets adhere to the site of injury in the blood vessel. Thrombin isactivated by platelet adherence and then acts to fully activateplatelets, enhance their adhesion and to release factor V from theplatelet as granules. Thrombin on the surface of activated plateletsactivates factors V, VIII and XI, with subsequent activation of factorIX. The tenase complex (factors IXa, VIIIa and calcium) now is presenton platelets where factor Xa can be produced and can generate anotherprothrombinase complex on the platelet so that there can be large-scaleproduction of thrombin (also called the thrombin burst). Propagation,the third step, is a combination of activation of the prothrombinasecomplexes that allow large amounts of thrombin to be generated fromprothrombin. More platelets can be recruited, as well as activation offibrin polymers and factor XIII.

Natural Anticoagulant Mechanisms

Platelet activation and coagulation normally do not occur within anintact blood vessel. Thrombosis (meaning a pathological process in whicha platelet aggregate and/or a fibrin clot occludes a blood vessel) isprevented by several regulatory mechanisms that require a normalvascular endothelium. Prostacyclin (PGI2), a metabolite of arachidonicacid synthesized by endothelial cells, inhibits platelet aggregation andsecretion. Antithrombin is a plasma protein that inhibits coagulationfactors of the intrinsic and common pathways. Heparan sulfateproteoglycans synthesized by endothelial cells stimulate the activity ofantithrombin. Protein C is a plasma zymogen homologous to Factors II,VII, IX, and X. Activated protein C in combination with its nonenzymaticcofactor (Protein S) degrades cofactors Va and VIIIa and thereby greatlydiminishes the rate of activation of prothrombin and factor X. Protein Cis activated by thrombin only in the presence of thrombomodulin, anintegral membrane protein of endothelial cells. Like antithrombin,protein C appears to exert an anticoagulant effect in the vicinity ofintact endothelial cells. Tissue factor pathway inhibitor (TFPI), whichis found in the lipoprotein fraction of plasma, when bound to factor Xa,inhibits factor Xa and the factor VIIa-tissue factor complex.

Thrombosis

Thrombosis refers to the formation of a thrombus, meaning a blood clotcomprising platelets, fibrin, leukocytes, and red blood cells locatedwithin a vascular lumen (Rubin's Pathology, Raphael Rubin and David S.Strayer, ed., 5th Ed., Lippincott Williams & Wilkins: 2008, page 233). Athrombus is distinct from a typical blood clot. While a blood clotresults from activation of the coagulation cascade, a thrombus alsoinvolves adherence and aggregation of platelets, participation ofcellular elements of the immune system, and active participation ofendothelial cells of the blood vessel (Id.).

Before injury to a blood vessel, circulating platelets are in anonadherent state. Injury activates platelet adhesiveness, after whichplatelets bind to one another to form an aggregate of activatedplatelets (platelet thrombus) (Id. at 394). These platelet aggregatesocclude injured small vessels and prevent leakage of blood. Onceplatelets are stimulated to adhere to the vessel wall, their granularcontents are released, in part by contraction of the plateletcytoskeleton. In turn, these granules promote aggregation of otherplatelets. Platelet adhesion is enhanced by release of subendothelialvon Willebrand factor, which is adhesive for Gp1b platelet membraneprotein and for fibrinogen. Activated platelets also release ADP andthromboxane A2, a product of arachidonic acid metabolism, which recruitadditional platelets to the process. The platelet membrane proteincomplex GpIIb-IIIc binds to fibrinogen, thereby forming fibrinogenbridges between platelets, enhancing aggregation, and stabilizing thenascent thrombus. Activated platelets in turn release factors thatinitiate coagulation, thus forming a complex thrombus on the vesselwall. Thrombin itself stimulates further release of platelet granulesand subsequent recruitment of new platelets.

Arterial Thrombosis

The coronary, cerebral, mesenteric, and renal arteries, and arteries ofthe lower extremities, are the vessels most commonly involved in anarterial thrombosis due to atherosclerosis. Arterial thrombosis may alsooccur, however, as a result of other disorders, including inflammationof arteries (arteritis), trauma, and blood diseases. Thrombi are alsocommon in aneurysms (localized-dilations of (lie lumen) of the aorta andits major branches, in which the distortion of blood flow, combined withintrinsic vascular disease, promotes thrombosis (Id. at 233).

Risk factors for thrombosis in the arterial system include, withoutlimitation, immobilization after surgery or leg casting, obesity,advanced age, previous thrombosis, and cancer. The three factors thatare commonly associated with development of thrombosis are: (1) damageto the endothelium, usually by atherosclerosis, which disturbs theanticoagulant properties of the vessel wall and serves as a site oforigin for platelet aggregation and fibrin formation; (2) alteration inblood flow, whether from turbulence at the site of an aneurysm, sites ofarterial bifurcation, or slowing of blood flow in narrowed arteries; and(3) increased coagulability of the blood.

Since most arterial thrombi occlude the vessel in which they occur, theyoften lead to ischemic necrosis of tissue supplied by that artery, i.e.,an infarct. Infarction is the process by which coagulative necrosisdevelops in an area distal to the occlusion of an end-artery (Id. at239). Thrombosis of a coronary or cerebral artery results in myocardialinfarct (heart attack) or cerebral infarct (stroke), respectively (Id.at 234).

Myocardial infarcts can be transmural (through the entire wall) orsubendocardial. While a transmural infarct results from completeocclusion of a major extramural coronary artery, a subendocardialinfarction reflects prolonged ischemia caused by partially occludinglesions of the coronary arteries when the requirement for oxygen exceedsthe supply (Id. at 241).

Thrombosis in the Heart

In a similar manner to the arterial system, thrombosis in the heart candevelop on the endocardium. Endocardial injury and changes in blood flowin the heart may lead to a thrombus adhering to the underlying wall ofthe heart (mural thrombosis) (Id. at 234). Mural thrombosis may occur asa result of diseases such as myocardial infarction, atrial fibrillation,cardiomyopathy, and endocarditis. In myocardial infarction, adherentmural thrombi form in the left ventricular cavity over areas ofmyocardial infarction due to damaged endocardium and alterations inblood flow associated with a poorly functional or a dynamic segment ofthe myocardium. In atrial fibrillation, disordered atrial rhythm leadsto slower blood flow and impaired left atrial contractility, whichpredisposes to formation of mural thrombi in atria. In cardiomyopathy,primary myocardial diseases are associated with mural thrombi in theleft ventricle, due to, e.g., endocardial injury and alteredhemodynamics associated with poor myocardial contractility. Inendocarditis, small thrombi may also develop on cardiac valves, usuallymitral or aortic, that are damaged by a bacterial infection.Occasionally these small thrombi form in the absence of valve infectionson a mitral or tricuspid valve (for example, injured by systemic lupuserythrematosis, SLE). In chronic wasting states, large friable smallthrombi may appear on cardiac valves, possibly reflecting ahypercoagulable state. A major complication of thrombosis in the heartoccurs when fragments of the thrombus detach and become lodged in bloodvessels at distant sites (embolization) (Id at 234).

Venous Thrombosis

Deep venous thrombosis, which occurs when a thrombus becomes lodged inone of the deep venous systems of the leg, often results from one ormore of the same causative factors that favor arterial and cardiacthrombosis. Those factors are endothelial injury (e.g., trauma, surgery,childbirth), stasis (e.g., heart failure, chronic venous insufficiency,post-operative immobilization, prolonged bed rest) and a hypercoagulablestate (e.g., oral contraceptives, late pregnancy, cancer, inheritedthrombophilic disorders, advanced age, venous varicosities,phlebosclerosis) (Id. at 234-235).

Greater than 90% of venous thrombosis occur in deep veins of the legs,and have several potential fates. They may remain small and eventuallybecome lysed, posing no further threat to health. Many become organized,whereby a small organization of venous thrombi may be incorporated intothe vessel wall, and larger ones may undergo canalization, with partialrestoration of venous drainage. Venous thrombi may also result inpropagation, whereby they serve as a site of origination for furtherthrombosis and propagate proximally to involve the larger iliofemoralveins. Those venous thrombi that are large or those that have propagatedproximally are a significant hazard to life, since they may dislodge andbe carried to the lungs as pulmonary emboli (Id).

Thrombosis in the Brain

Thrombosis of a cerebral artery results in cerebral infarct, alsoreferred to as a stroke. the most common type of cerebral infarct is theischemic stroke, which may occur as a result of the blockage of anartery vein (Gomes et al., Handbook of Clinical Nutrition and Stroke(2013) Chapter 2, page 17). The term “stroke in evolution” as usedherein reflects propagation of a thrombus in the carotid or basilararteries, and describes the progression of neurologic symptoms while thepatient is under observation. The term “completed stroke” as used hereinrefers to a stable neurologic deficit resulting from a cerebral infarct(Rubin's Pathology, Raphael Rubin and David S. Strayer, ed., 5th Ed.,Lippincott Williams & Wilkins: 2008, page 1192).

The occlusion of different cerebral vessels results in diverseneurologic deficits caused by stroke. For example, occlusion or stenosisof an internal carotid artery affects the ipsilateral hemisphere, butthis can be offset by the variable collateral circulation through theanterior and posterior communicating arteries. Most often, occlusion ofa carotid artery produces infarcts restricted to all or some portion ofthe distribution of the middle cerebral artery. The consequences ofocclusion of the various branches of the circle of Willis depend on theconfiguration of the circle. For example, occlusion at the trifurcationof the middle cerebral artery deprives the parietal cortex ofcirculation and produces motor and sensory deficits. When the dominanthemisphere is involved, these lesions are commonly accompanied byapcomprisesia. An infarct of the lengthy and slender striate arteries,which originate from the proximal middle cerebral artery, oftentransects the internal capsule and produces hemiparesis or hemiplegia(Id.).

Infarction of the cerebral arteries may result from local ischemia or ageneralized reduction in blood flow. The latter often results fromsystemic hypotension (e.g., shock), and produces infarction in theborder zones between the distributions of the major cerebral arteries.If prolonged, severe hypotension can cause widespread brain necrosis.The occlusion of a single vessel in the brain (e.g., after an emboluscomprises lodged) causes ischemia and necrosis in a well-defined area.The occlusion of a large artery produces a wide area of necrosis.

Cerebral Venous Sinus Thrombosis

The cerebral veins empty into large venous sinuses, the most prominentof which is the sagittal sinus which accommodates the venous drainagefrom the superior portions of the cerebral hemispheres. If a patientdevelops a blood clot in a superficial or deep cerebral vein or venoussinus, hydrostatic pressure will increase upstream of the venous side ofthe capillary bed until ultimately water is forced through the capillarywalls and into the interstitium of adjacent brain tissue reliant on theaffected vein for normal fluid balance. This will eventually lead tohemorrhagic necrosis and vasogenic edema in the affected area. Venoussinus thrombosis in the brain is a potentially lethal complication ofsystemic dehydration, phlebitis, obstruction by a neoplasm, or sicklecell disease. Because venous obstruction causes stagnation upstream,abrupt thrombosis of the sagittal sinus results in bilateral hemorrhagicinfarctions of the frontal lobe regions. A more indolent occlusion ofthe sinus (e.g., due to invasion by a meningioma) permits therecruitment of collateral circulation through the inferior sagittalsinus (Id. at 1194).

Fibrinolytic Agents

One method of treating a thrombosis is with a thrombolytic agent thatbreaks down the fibrinogen and fibrin comprising the thrombus. Thesefibrinolytic agents (also referred to as plasminogen activators) can bebroadly classified into two groups: fibrin-specific agents; andnon-fibrin specific agents. Fibrin-specific agents include drugs such asalteplase (tPA), reteplase (recombinant plasminogen activator; r-PA),and tenecteplase, which produce limited plasminogen conversion in theabsence of fibrin (Ouriel K. A history of thrombolytic therapy. JEndovasc Ther. 2004 Dec. 11 Suppl 2:11128-133). Non-fibrin specificagents, including agents such as streptokinase, catalyze systemicfibrinolysis.

Fibrinolytic agents can be administered systemically or directly to thearea of the thrombus. Treatment of acute myocardial infarction and acuteischemic stroke typically involves systemic delivery of the fibrinolyticagents (Hoffman R, Benz E J, Shattil S J, et al. Antithrombotic Drugs.In: Hematology: Basic Principles and Practice. 5th ed. Philadelphia,Pa.: Churchill Livingston Elsevier; 2008. chap 137).

Fibrinolytic agents can be used to treat several types of vascularobstruction conditions such as acute myocardial infarction, pulmonaryembolism, deep vein thrombosis, acute ischemic stroke, and peripheralarterial disease. However, the use of fibrinolytic therapy comprisesmany drawbacks, including, without limitation, allergic reactions,embolism, stroke, and reperfusion arrhythmias, among others. One of themore serious complications is hemorrhage, such as intracranialhemorrhage (ICH) (See, Mehta R H, Cox M, Smith E E, et al., Race/Ethnicdifferences in the risk of hemorrhagic complications among patients withischemic stroke receiving thrombolytic therapy. Stroke. 2014 August 45(8):2263-9).

In addition, fibrinolytic agents have limited efficacy in certainconditions. For example, although tPA is an accepted treatment fortreatment of acute ischemic stroke, the drug's ability to recanalize avessel is poor in some cases. In proximal occlusions, for example, lowrecanalization rates are observed (8% recanalization in ICA occlusions),while in more distal occlusions higher rates of recanalization areobserved (26% in M1 occlusions, 35% in M2 occlusions, and 40% in M3occlusions) (Holodinsky, J. K. et al., Curr Neurol Neurosci Rep (2016)16:42). Studies have shown that tPA is relatively ineffective forocclusions in the proximal anterior circulation, such as carotid Tocclusions, carotid L occlusions, and M1/M2 occlusions of the MCA, whichaccount for about one third of cases of acute ischemic stroke (Id.).Furthermore, the effectiveness of fibrinolytic agents, such as tPA, isdependent upon early administration. For example, a meta-analysis ofseveral randomized trials of tPA administration after stroke onsetrevealed that a treatment delay of more than 4.5 hours resulted in nodifference between tPA treatment and placebo treatment. This result maybe due, in part, to a reduced chance of thrombus resolution as timepasses and fibrin crosslinking occurs within the thrombus (Id.).

In some instances, fibrinolytic agents cannot be used at all. Forexample, the presence of active internal bleeding, recent intracranialor intraspinal trauma, a past or present bleeding disorder, uncontrolledhypertension, and pregnancy are all absolute contraindications offibrinolytic agents.

Mechanical Endovascular Intervention

The current standard for therapeutic recanalization and reperfusion invascular disease and acute stroke is to perform mechanical endovascularinterventions via a transfemoral approach, meaning, starting a catheterin the femoral artery at the groin, proceeding through the aorta andcarotid artery to the affected blood vessel. All existing devices aredesigned to be used from this starting point and surgeons are mostfamiliar and comfortable with this route.

Mechanical Endovascular Intervention in Coronary Artery Disease (CAD)

Percutaneous Coronary Intervention (PCI)

Percutaneous coronary intervention (PCI) is a nonsurgical method forcoronary artery revascularization. PCI methods include balloonangioplasty, coronary stenting, atherectomy (devices that ablateplaque), thrombectomy (devices that remove clots from blood vessels) andembolic protection (devices that capture and remove embolic debris).

Balloon Angioplasty

Balloon angioplasty involves advancing a balloon-tipped catheter to anarea of coronary narrowing, inflating the balloon, and then removing thecatheter after deflation. Balloon angioplasty can reduce the severity ofcoronary stenosis, improve coronary flow, and diminish or eliminateobjective and subjective manifestations of ischemia (Losordo D. W. etal. Circulation 1992 December 86(6):1845-58). The mechanism of balloonangioplasty action involves three events: plaque fracture, compressionof the plaque, and stretching of the vessel wall. These lead toexpansion of the external elastic lumina and axial plaque redistributionalong the length of the vessel (Losordo D. W. et al. Circulation 1992December 86(6):1845-58).

Coronary Stenting

Coronary stents are metallic scaffolds that are deployed within adiseased coronary artery segment to maintain wide luminal patency. Theywere devised as permanent endoluminal prostheses that could sealdissections, create a predictably large initial lumen, and prevent earlyrecoil and late vascular remodeling (Krajcer Z. and Howell M. H. TexHeart Inst J. 2000; 27(4): 369-385).

Drug-eluting stents (DESs) elute medication to reduce restenosis (therecurrence of abnormal narrowing of a blood vessel) within the stents.Local release of rapamycin and its derivatives or of paclitaxel from apolymer matrix on the stent during the 30 days after implantationcomprises been shown to reduce inflammation and smooth muscle cellproliferation within the stent, decreasing in-stent late loss of luminaldiameter from the usual 1 mm to as little as 0.2 mm (Stone G. W. et al.N Engl J Med. 2007 Mar. 8. 356(10):998-1008). This dramatically lowersthe restenosis rate after initial stent implantation or after secondaryimplantation of a DES for an in-stent restenosis (Stone G. W. et al. NEngl J Med. 2007 Mar. 8. 356(10):998-1008).

Coronary stents are used in about 90% of interventional procedures.Stent-assisted coronary intervention comprises replaced coronary arterybypass graft (CABG) as the most common revascularization procedure inpatients with coronary artery disease (CAD) and is used in patients withmulti-vessel disease and complex coronary anatomy (Kalyanasundaram A. etal. Medscape Dec. 16, 2014; article 164682;emedicine.medscape.com/article/164682-overview#a3).

Atherectomy

The directional coronary atherectomy (DCA) catheter was first used inhuman peripheral vessels in 1985 and in coronary arteries in 1986. Inthis procedure, a low-pressure positioning balloon presses a windowedsteel housing against a lesion; any plaque that protrudes into thewindow is shaved from the lesion by a spinning cup-shaped cutter andtrapped in the device's nose cone (Hinohara T. et al. Circulation 1990March 81(3 Suppl): IV79-91).

Rotational atherectomy uses a high-speed mechanical rotationalstainless-steel burr with a diamond chip-embedded surface. The burr isattached to a hollow flexible drive shaft that permits it to be advancedover a steerable guide wire with a platinum coil tip. The drive shaft isencased within a Teflon® sheath through which a flush solution is pumpedto lubricate and cool the drive shaft and burr. A compressed air turbinerotates the drive shaft at 140,000-200,000 rpm during advancement acrossa lesion (Hinohara T. et al. Circulation 1990 March 81(3 Suppl):IV79-91).

Laser Ablation

In laser ablation, an intense light beam travels via optical fiberswithin a catheter and enters the coronary lumen. After the target lesionis crossed with the guide wire, the laser catheter is advanced to theproximal end of the lesion. Blood and contrast medium are removed fromthe target vessel by flushing with saline before activating the laser(Kalyanasundaram A. et al. Medscape Dec. 16, 2014; article 164682;emedicine.medscape.com/article/164682-overview#a3).

Mechanical Thrombectomy

Intracoronary thrombi may be treated with mechanical thrombectomydevices. These include rheolytic, suction and ultrasonic thrombectomydevices.

In rheolytic thrombectomy, high-speed water jets create suction via theBernoulli-Venturi effect. The jets exit orifices near the catheter tipand spray back into the mouth of the catheter, creating a low-pressureregion and intense suction. This suction pulls surrounding blood,thrombus, and saline into the tip opening and propels particlesproximally through the catheter lumen and out of the body(Kalyanasundaram A. et al. Medscape Dec. 16, 2014; article 164682;emedicine.medscape.com/article/164682-overview#a3).

The catheters used for suction thrombectomy act via manual aspiration.These catheters are advanced over a wire to the intracoronary thrombusthen passed through the thrombus while suction is applied to a hole inthe catheter tip. Large intact thrombus fragments can be removed bymeans of this technique (Kalyanasundaram A. et al. Medscape Dec. 16,2014; article 164682;emedicine.medscape.com/article/164682-overview#a3).

Ultrasonic thrombectomy involves the use of ultrasonic vibration toinduce cavitation that can fragment a thrombus into smaller components(Choi S. W. et al. J. Intery Cardiol. 2006 Feb. 19(1): 87-92).

Embolization Protection

Embolization (the passage of an embolus (blood clot) within the bloodstream) can be caused by the manipulation of guidewires, balloons, andstents across complex atherosclerotic carotid artery lesions (Krajcer Z.and Howell M. H. Tex Heart Inst J. 2000; 27(4): 369-385). Severaldevices have been developed to trap such embolic material and remove itfrom the circulation.

The PercuSurge Guardwire is a device that consists of a 0.014- or0.018-inch angioplasty guidewire constructed of a hollow nitinolhypotube. Incorporated into the distal wire segment is an inflatableballoon capable of occluding vessel flow. The proximal end of the wireincorporates a Microseal™ that allows inflation and deflation of thedistal occlusion balloon. When the Microseal adapter is detached, theocclusion balloon remains inflated, at which time angioplasty andstenting are performed. An aspiration catheter can be advanced over thewire into the vessel, and manual suction is applied to retrieveparticulate debris (Krajcer Z. and Howell M. H. Tex Heart Inst J. 2000;27(4): 369-385).

The Medicorp device consists of a protection balloon and a dilationballoon that can be used over a 0.014-inch coronary guidewire. Occlusionabove the lesion and below the lesion creates a dilation zone without aflow, which is aspirated and cleared of atherosclerotic debris (KrajcerZ. and Howell M. H. Tex Heart Inst J. 2000; 27(4): 369-385).

Endovascular Treatment of Abdominal Aortic Aneurysms (AAA)

Two endoluminal AAA exclusion stent graft systems have received FDAapproval: (i) the Ancure™ Endograft System (Guidant/EVT; Menlo Park,Calif.); and (ii) the AneuRx™ device (Medtronic AVE; Santa Rosa, Calif.)(Krajcer Z. and Howell M. H. Tex Heart Inst J. 2000; 27(4): 369-385).Both are over-the-wire systems that require bilateral femoral arteryaccess.

The Ancure™ stent graft is an unsupported, single piece of woven Dacron®fabric. The graft is bifurcated and comprises no intra-graft junctions.The main device is delivered through a 24-Fr introducer sheath; a 12-Frsheath is required to facilitate the deployment of the contralateraliliac limb. The graft is attached via a series of hooks that are locatedat the proximal aortic end and at both iliac ends. The hooks are seatedtransmurally (passing through the vessel wall) in the aorta and theiliac arteries, initially by minimal radial force, and then affixed bylow-pressure balloon dilation. Radiopaque markers are located on thebody of the graft for correct alignment and positioning (Krajcer Z. andHowell M. H. Tex Heart Inst J. 2000; 27(4): 369-385).

The AneuRx™ device is a modular 2-piece system composed of a mainbifurcation segment and a contralateral iliac limb. The graft is made ofthin-walled woven polyester that is fully supported by a self-expandingnitinol exoskeleton. Attachment is accomplished by radial force at theattachment sites, which causes a frictional seal. The main bifurcatedbody is delivered through a 21-Fr sheath, and the contralateral limbrequires a 16-Fr sheath. The body of the graft comprises radiopaquemarkers that facilitate correct alignment and positioning (Krajcer Z.and Howell M. H. Tex Heart Inst J. 2000; 27(4): 369-385).

Mechanical Endovascular Neurointervention Mechanical Thrombectomy

Mechanical thrombectomy (excision of a clot from a blood vessel) devicesremove occluding thrombi (blood clots) from the target vessel by acatheter. Subgroups include: (1) suction thrombectomy devices thatremove occlusions from the cerebral vessels by aspiration (ProximalThrombectomy) and (2) clot removal devices that physically seizecerebral thrombi and drag them out of the cerebral vessels (DistalThrombectomy) (Gralla J. et al. Stroke 2006; 37: 3019-24; Brekenfeld C.et al. Stroke 2008; 39: 1213-9).

Proximal Endovascular Thrombectomy

Manual suction thrombectomy is performed by moving forward an aspirationcatheter at the proximal surface of the thrombus (Singh P. et al. JNeurosci Rural Pract. 2013 July-September; 4(3): 298-303). Manualaspiration is then carried out and the aspiration catheter is taken backunder continuous negative pressure. The Penumbra System™ (Penumbra,Almeda, Calif. USA), a variation of the manual proximal aspirationmethod, comprises a dedicated reperfusion catheter attached to a pumpingsystem applying constant aspiration. A second retriever device issimilar to a stent and is utilized to take out the resistant clot (SinghP. et al. J Neurosci Rural Pract. 2013 July-September; 4(3): 298-303).The time window for neuroradiological intervention is 8 hours afterstroke onset in patients not eligible for intravenous thrombolysis or inpatients where intravenous thrombolysis was unsuccessful (Singh P. etal. J Neurosci Rural Pract. 2013 July-September; 4(3): 298-303).

The Penumbra System™ comprises been examined in a number of clinicaltrials. The Penumbra Pivotal Stroke Trial was a prospective, single-arm,multicenter study that recruited 125 stroke patients (mean NIHSS 18)within 8 hours of symptom onset and was successful in 81.6% of treatedvessels (Penumbra Pivotal Stroke Trial Investigators: The Penumbrapivotal stroke trial: Safety and effectiveness of a new generation ofmechanical devices for clot removal in intracranial large vesselocclusive disease. Stroke 2009; 40: 2761-8). However, a good clinicaloutcome at 90 days was attained in only 25% of patients and in 29% ofpatients with successful recanalization (the process of restoring flowto or reuniting an interrupted channel such as a blood vessel) of thetarget vessel (Penumbra Pivotal Stroke Trial Investigators: The penumbrapivotal stroke trial: Safety and effectiveness of a new generation ofmechanical devices for clot removal in intracranial large vesselocclusive disease. Stroke. 2009; 40: 2761-8). Poor clinical resultsoccurred despite comparatively better recanalization rates as evidencedby a mortality rate of 32.8% and the occurrence of symptomaticintracerebral hemorrhage (ICH) in 11.2% (Penumbra Pivotal Stroke TrialInvestigators: The penumbra pivotal stroke trial: Safety andeffectiveness of a new generation of mechanical devices for clot removalin intracranial large vessel occlusive disease. Stroke. 2009; 40:2761-8).

Distal Endovascular Thrombectomy

Distal thrombectomy is a technically difficult procedure (Singh P. etal. J Neurosci Rural Pract. 2013 July-September; 4(3): 298-303). Anumber of clinical studies have been carried out using the MERCI(Mechanical Embolus Removal in Cerebral Ischemia) Retriever® device(Concentric Medical, Mountain View, USA), which was the earliest distalthrombectomy device approved by the United States Food and DrugAdministration (FDA) (Singh P. et al. J Neurosci Rural Pract. 2013July-September; 4(3): 298-303). In the initial stage of the procedure,the occlusion site must be traversed with a microcatheter so as todeploy the device beyond the thrombus. The MERCI Retriever® device ispulled back into the thrombus and positioned within the clot. Next, theMERCI Retriever® and the trapped clot are withdrawn, initially into thepositioning catheter and then out of the patient's body (Singh P. et al.J Neurosci Rural Pract. 2013 July-September; 4(3): 298-303). Proximalballoon occlusion by means of a balloon guide catheter and aspirationduring retrieval of the Merci device is done for the majority of casesin order to prevent thromboembolic complications (Nogueira R. G. et al.Am J Neuroradiol. 2009; 30: 649-61; Nogueira R. G. et al. Am JNeuroradiol. 2009; 30: 859-7). During in vivo experimental studies, thedistal technique was shown to be more efficient than proximal manualaspiration (Gralla J. et al. Stroke 2006; 37: 3019-24).

The MERCI Retriever® clinical trial was a 25-site, uncontrolled,technical efficacy trial (Smith W. S. et al. Stroke 2005; 36: 1432-8).The trial incorporated 151 patients with occlusion of the internalcarotid artery or vertebral and basilar arteries, who did not qualifyfor intra-arterial therapy (IAT) within 8 hours of symptom onset (SmithW. S. et al. Stroke 2005; 36: 1432-8). Successful recanalization wasaccomplished in 46%, with excellent clinical outcome in 27.7% ofpatients (Smith W. S. et al. Stroke 2005; 36: 1432-8). Successfulrecanalization was linked with distinctly better clinical outcomes.Average procedure time was 2.1 hours, with clinically noteworthyprocedural complications occurring in 7.1% and a rate of symptomaticintracranial hemorrhage (ICH) occurring in 7.8% of patients (Smith W. S.et al. Stroke 2005; 36: 1432-8). Despite good clinical outcome,limitations of this device include operator learning curve, the need totraverse the occluded artery to deploy the device distal to theocclusion, the duration required to perform multiple passes with thedevice, clot fragmentation and passage of an embolus within thebloodstream (Meyers P. M. et al. Circulation 2011; 123: 2591-2601).

Self-Expanding Stents

Until recently, intracranial stenting was restricted to off-label use ofballoon-mounted stents intended for cardiac circulation (Singh P. et al.J Neurosci Rural Pract. 2013 July-September; 4(3): 298-303). Thesestents are not ideal for treating intracranial disease due to theirrigidity which makes navigation in the convoluted intracranial vesselsdifficult (Singh P. et al. J Neurosci Rural Pract. 2013 July-September;4(3): 298-303). Self-expanding intracranial stents permit stenting inacute stroke that is unmanageable with conventional treatment regimens.The clot occluding the vessel is outwardly displaced by the side of thevessel wall and becomes trapped in the interstices of a self-expandingstent (SES). Wingspan™ (Stryker), Neuroform® (Stryker, Kalamazoo,Mich.), and Cordis Enterprise™ (Cordis Neurovascular, Fremont, Calif.)self-expanding stenting systems have improved steering, cause a reducedamount of vasospasm, and cause a reduced amount of side-branchocclusions as compared to balloon-inflated stents (Singh P. et al. JNeurosci Rural Pract. 2013 July-September; 4(3): 298-303). Drawbacks ofthis method include delayed in-stent thrombosis, the use of plateletinhibitors which may cause intracerebral hemorrhage (ICH) and perforatorocclusion from relocation of the thrombus after stent placement(Samaniego E. A. et al Front Neurol. 2011; 2: 1-7; Fitzsimmons B. F. etal. Am J Neuroradiol. 2006; 27: 1132-4; Levy E. I. et al. Neurosurgery2006; 58: 458-63; Zaidat O. O. et al. Stroke 2008; 39: 2392-5).

Retrievable Thrombectomy Stents

Retrievable thrombectomy stents are self-expandable, re-sheathable, andre-constrainable stent-like thrombectomy devices which combine theadvantages of intracranial stent deployment with immediate reperfusionand subsequent retrieval with definitive clot removal from the occludedartery (Singh P. et al. J Neurosci Rural Pract. 2013 July-September;4(3): 298-303). Removal of the device circumvents the drawbacksassociated with permanent stent implantation. These include therequirement for double anti-platelet medication, which potentially addsto the risk of hemorrhagic complications, and the risk of in-stentthrombosis or stenosis. The application of retrievable thrombectomystents is analogous to that of intracranial stents. Under generalanesthesia, using a transfemoral approach, a guide catheter ispositioned in the proximal internal carotid artery. A guide wire isadvanced coaxially over a microcatheter within the blocked intracranialvessel and navigated past the thrombus. The microcatheter is thenadvanced over the wire through the clot, and the guide wire issubstituted for the embolectomy device (Id.). The revascularizationdevice is placed with the middle third of the device residing within thethrombus formation. The radial force of the stent retriever is able tocreate a channel by squeezing the thrombus and is able to partiallyrestore blood flow to the distal territory in the majority of cases,producing a channel for a temporary bypass (Id). The device is usuallyleft in place for an embedding time of up to 10 minutes, permittingentrapment of the thrombus within the stent struts. To extract thethrombus, the unfolded stent and the microcatheter are slowly draggedinto the guide catheter with flow reversal by continuous aspiration witha 50-ml syringe from the guide catheter (Id.). The designs of thesestents differ in terms of radial strength, design of the proximal anddistal stent aperture, stent cell design, material and supplementaryintraluminal struts (Mordasini P. et al. Am J Neuroradiol 2011; 32:294-300; Brekenfeld C. et al. Am J Neuroradiol. 201; 2: 1269-73;Mordasini P. et al. Am J Neuroradiol. 2013; 34: 153-8).

Blood Vessels Used for Mechanical Intervention Femoral Artery

The femoral artery is the main artery that provides oxygenated blood tothe tissues of the leg. It passes through the deep tissues of thefemoral (or thigh) region of the leg parallel to the femur.

The common femoral artery is the largest artery found in the femoral(thigh) region of the body. It begins as a continuation of the externaliliac artery at the inguinal ligament which serves as the dividing linebetween the pelvis and the leg. From the inguinal ligament, the femoralartery follows the medial side of the head and neck of the femurinferiorly and laterally before splitting into the deep femoral arteryand the superficial femoral artery.

The superficial femoral artery flexes to follow the femur inferiorly andmedially. At its distal end, it flexes again and descends posterior tothe femur before forming the popliteal artery of the posterior knee andcontinuing on into the lower leg and foot. Several smaller arteriesbranch off from the superficial femoral artery to provide blood to theskin and superficial muscles of the thigh.

The deep femoral artery follows the same path as the superficial branch,but follows a deeper path through the tissues of the thigh, closer tothe femur. It branches off into the lateral and medial circumflexarteries and the perforating arteries that wrap around the femur anddeliver blood to the femur and deep muscles of the thigh. Unlike thesuperficial femoral artery, none of the branches of the deep femoralartery continue into the lower leg or foot.

Like most blood vessels, the femoral artery is made of several distincttissue layers that help it to deliver blood to the tissues of the leg.The innermost layer, known as the endothelium or tunica intima, is madeof thin, simple squamous epithelium that holds the blood inside thehollow lumen of the blood vessel and prevents platelets from sticking tothe surface and forming blood clots. Surrounding the tunica intima is athicker middle layer of connective tissues known as the tunica media.The tunica media contains many elastic and collagen fibers that give thefemoral artery its strength and elasticity to withstand the force ofblood pressure inside the vessel. Visceral muscle in the tunica mediamay contract or relax to help regulate the amount of blood flow.Finally, the tunica externa is the outermost layer of the femoral arterythat contains many collagen fibers to reinforce the artery and anchor itto the surrounding tissues so that it remains stationary.

The femoral artery is classified as an elastic artery, meaning that itcontains many elastic fibers that allow it to stretch in response toblood pressure. Every contraction of the heart causes a sudden increasein the blood pressure in the femoral artery, and the artery wall expandsto accommodate the blood. This property allows the femoral artery to beused to detect a person's pulse through the skin (See, e.g., TheCardiovascular System at a Glance, 4th Edition, Philip I. Aaronson,Jeremy P. T. Ward, Michelle J. Connolly, November 2012, © 2012,Wiley-Blackwell, Hoboken, N.J.).

Use of the Femoral Artery for Endovascular Procedures

Endovascular diagnostic and therapeutic procedures are generallyperformed through the femoral artery. Some of the reasons for thisgeneralized approach include its location, easy approach for punctureand hemostasis, low rate of complications, technical ease, wideapplicability and relative patient comfort (Alvarez-Tostado J. A. et al.Journal of Vascular Surgery 2009; 49(2): 378-385). Femoral puncture alsoallows access to virtually all of the arterial territories and affordsfavorable ergonomics for the operator in most instances (Alvarez-TostadoJ. A. et al. Journal of Vascular Surgery 2009; 49(2): 378-385).

Brachial Artery

The brachial artery is a major blood vessel located in the upper arm andis the main supplier of blood to the arm and hand. It continues from theaxillary artery at the shoulder and travels down the underside of thearm. Along with the medial cubital vein and bicep tendon, it forms thecubital fossa, a triangular pit on the inside of the elbow. Below thecubital fossa, the brachial artery divides into two arteries runningdown the forearm: the ulnar and the radial; the two main branches of thebrachial artery. Other branches of the brachial artery include theinferior ulnar collateral, profunda brachii, and superior ulnar arteries(See, e.g., The Cardiovascular System at a Glance, 4th Edition, PhilipI. Aaronson, Jeremy P. T. Ward, Michelle J. Connolly, November 2012, ©2012, Wiley-Blackwell, Hoboken, N.J.).

Use of the Brachial Artery for Endovascular Procedures

Brachial artery access is a critical component of complex endovascularprocedures, especially in instances where femoral access is difficult orcontraindicated, such as the absence of palpable femoral pulses, severecommon femoral occlusive disease, recent femoral intervention or surgeryor femoral aneurysms/pseudoaneurysms. It is a straightforward procedurewith a high success rate for percutaneous cannulation (Alvarez-TostadoJ. A. et al. Journal of Vascular Surgery 2009; 49(2): 378-385). However,there is a general reluctance to puncture the right brachial artery dueto the need to navigate through the innominate artery and arch and dueto the risk for complications such as direct nerve trauma and ischemicocclusion resulting in long-term disability (Alvarez-Tostado J. A. etal. Journal of Vascular Surgery 2009; 49(2): 378-385; Cousins T. R. andO'Donnell J. M. AANA Journal 2004; 72(4): 267-271).

Need for New Endovascular Thrombectomy Devices

Mechanical endovascular neurointerventions are the current standard forthe treatment of acute stroke. Several independent clinical trials have,however, identified significantly different clinical outcomes inpatients when treated with different endovascular techniques andthrombectomy devices (Papanagiotou, P., and White, C. J., EndovascularReperfusion Strategies for Acute Stroke, JACC: CardiovascularInterventions, 2016, Vol. 9, No. 4, pg 307). For example, stentretriever devices generally have been identified as providing higherrecanalization rates with a reduced recanalization time and lowercomplication rates when compared to first generation mechanicalrecanalization devices such as the Merci device and the Penumbraaspiration system (Id. at 315).

Despite the potential to diminish procedure time and to improverecanalization rates, drawbacks to using these devices remain. Forexample, the TREVO 2 study (Thrombectomy Revascularisation of LargeVessel Occlusions in AIS) was an open label, multi-center trialevaluating the efficacy of the Trevo Pro retriever (StrykerNeurovascular, Fremont, USA) with the Merci device in patients withlarge vessel ischemic stroke (Nogueira R. G. et al. Lancet 2012; 380:1231-40). Symptomatic intra cranial hemorrhage (ICH) occurred in 6.8% inthe Trevo group and in 8.9% of the Merci group, with mortality rates of33% and 24% respectively. The outcome of this trial suggests that thereare unique mechanical mechanisms of action and consequently dissimilarsuccess and efficacy rates depending on the thrombectomy approachesapplied (Singh P. et al. J Neurosci Rural Pract. 2013 July-September;4(3): 298-303).

Furthermore, some blood vessel occlusions are resistant torecanalization by a particular thrombectomy device due to thecharacteristics of the thrombus (e.g. a “hard” thrombus) and theparticular blood vessel where the occlusion is located (Papanagiotou,P., and White, C. J., Endovascular Reperfusion Strategies for AcuteStroke, JACC: Cardiovascular Interventions, 2016, Vol. 9, No. 4, pg.315).

Thus, at present, there does not appear to be a universally superiormechanical thrombectomy device that provides sufficient aspiration forcewithout obstructing aspiration, is manageable in terms of size andflexibility, and is quick/easy to remove while preventing emboli fromgoing to end organs. There thus remains a need for mechanicalthrombectomy devices and strategies. The disclosed invention addressesthis unmet need.

SUMMARY OF THE INVENTION

The present invention is an element is a devise which provides a safeand reliable means of applying a simultaneous combination of irrigation,aspiration and maceration to a thrombi or similar material. In orderfurther the device's purpose of safely and effectively performingthrombectomy or the like. More particularly, the present inventiondiscloses a “string length adjustment mechanism” for a lasso, namely amechanism to allow more lengths of string into “system”, oralternatively to shorten the length of available string in the system,namely a ratchet, or a reel among others. Said system is part of afilter assembly that is openable and closeable while in use within abodily vessel, by deployment of a string or wire arranged such that alasso or drawstring type cincture is affected

According to one aspect, the described invention provides anendovascular device including a semi-permeable flared filter orfiltered-tipped catheter for capturing emboli while allowing passagetherethrough of blood cells and serum, wherein the flared opening of thefilter may be opened or closed by the user while deployed within avessel. The present invention comprises a staffed conical filter havingat least one string or wire capable of opening or collapsing said filterin the manner of a lasso or drawstring, with a string that communicatesfrom an attachment point around the circumference of the filter opening,disposed within at least one channel or set of hoops about the rim ofthe filter, and down catheter element, and out a side hole.Alternatively, the string may have a small loop through which the wiresubsequently passes after said wire goes around the entire circumferenceof the distal segment of the filter, in the manner of a typical lasso.The string or wire is expanded or contracted via a reeling or ratchetingmechanism through which it passes to outside a patient's body. A numberof variant embodiments are disclosed, each implementing the lassoprinciple.

For disclosure purposes the term rim of the filter is a zone on asegment of the present invention's filter element which is capable ofexpanding maximally to abut the walls of a target vessel. The termattachment point means a zone on a region on the catheter around thecircumference of the filter opening, at the base of the cone of thefilter, at which the filter is adhered circumferentially to thecatheter. The size of said segment and the size of said rim depend uponthe size of the device of the present invention. In the preferredembodiment, the attachment point is a circular area of approximately0.01 mm to 3 cm in length, diameter and the rim is a cylindrical area of0.01 mm to 6 cm in length and a diameter of 0.5 mm-7 cm when the filteris fully expanded. The only limitation in location or size of either therim or point, is mechanical. Said size or location must not prevent thefilter element of the present invention from expanding or collapsing.

The present invention has numerous embodiments. These include a flared,semi-permeable filters, filtered-tipped catheters, reverse-flaredfilters, internal lumens, external lumens, among others. However, thepresent invention is simply the use of a lasso-type mechanism to openand close a catheter filter.

More particularly, the present invention has the following novelcharacteristics: combining the simultaneous irrigation, aspiration, andmaceration; combining the simultaneous irrigation and aspiration toreverse flow, independent of maceration; combining the simultaneousirrigation and aspiration to reverse flow, independent of maceration,and retrieving clots by removing the bulk of the clot, and the inducedflow reversal by the combination of simultaneous irrigation andaspiration make sure any clot pieces that break free are removed fromthe body via the aspiration, rather than embolizing distally and causingpermanent tissue ischemia; using a balloon mounted aspiration catheter,designed to use at the face of an arterial thrombus, to occlude a vesseland facilitate flow reversal via aspiration and simultaneous distalirrigation; using a filter-tip aspiration catheter—for use in mostvenous and dialysis av graft de-clot cases; using the present withaddition of IVUS to monitor flow and clot build-up at the tip of thecatheter (particularly the preferred embodiment of the presentinvention, at the catheter tip in the filter-tip aspiration catheterversion); using the present invention (particularly in the aspirationcatheter, balloon mounted, and/or filter-tip aspiration catheter) withthe addition of a vibrational wire in or distal to the catheter, tobreak up the clot to avoid the aspirating catheter becoming clogged withlarge pieces of clot; and using the sinusoidal hypo-tube embodiment ofthe present invention that has an eggbeater like-maceration effect,while simultaneously irrigating into and beyond the clot and aspiratingto remove the clot. The present invention's vibrational wire may be usedwith any aspiration catheter and/or balloon mounted aspiration catheteras well.

The present invention's filter-tip aspirator catheter can also be usedin select cases of peripheral arterial thrombectomies. The prerequisitein such cases is the ability to access the artery downstream from aclot. This is usually not possible for arterial emboli in the brain, butmay be possible for arteries in arms and legs. A non-limiting example isan axillary artery embolus/thrombus, where a person of ordinary skillcan obtain access proximal to the clot from femoral access, and/or aperson of ordinary skill can also access distally (downstream) via abrachial or radial artery approach.

A medical device according to the present invention generally includes acombination of three elements from the prior art, namely irrigation,aspiration and maceration for the purpose of safely and effectivelyperforming thrombectomy, usually involving removal of thrombi (bloodclots). More particularly, in preferred embodiment the present inventionhas a single switch that simultaneously starts a pump for irrigation, avacuum for aspiration, and a rotational element for rotationalmaceration. Alternatively, if the present invention is used in aninterventional suite or other environment which already has a “powerinjector” that can inject irrigation, then the preferred embodiment ofthe present invention would include a remote-control element to allowexisting irrigation devices to be activated and deactivatedsimultaneously with the aspiration and maceration elements of thepresent invention. Additionally, the present invention may optionally beequipped to allow sequential/stepwise activation of each of theirrigation, aspiration and maceration features of the current invention.

To clarify, the present invention is a device and a method for usingsaid device to overcome the medical difficulties associated with vesselcollapse during a clot removal procedure. More particularly, the presentinvention introduces fluids such as a saline solution to a target clotsimultaneously with the remove of parts of said target clot to maintainpressure inside a vessel from which said target clot is removed.

More specifically, removing target clots from a vessel is best donewithout damaging said vessel. Optimal devices and method remove saidtarget clots by using existing access to said vessels, particularlyother existing vessels. Removing said target clots using said optimaldevices and methods have three significant difficulties. First saidtarget clots are too large to use existing vessels as exit passages. Thecurrent invention, like other elements of prior art, uses mechanicalmeans to reduce said target clots into two or more elements so as toallow the existing vessels to be used as exit passages.

This process results in the second significant difficulty, which is saidtwo or more elements when separated from said target move in saidexisting vessels to cause difficulties elsewhere in body connected tosaid vessel. This second difficulty has been ameliorated by aspiratingthe said two or more elements. The current invention, like otherelements of prior art, uses aspiration to ameliorate said seconddifficulty.

Said aspirating causes a third difficulty which is the collapse of saidvessel. The present invention unlikely any prior are prevents saidvessel collapse by replacing the mass of the target clot with materialsuch as saline solution while simultaneously which removing said mass ofthe target clot.

More particularly, the present invention simultaneously irrigatesaspirates and cuts clots. The irrigation both expands the vesselsurrounding a targeted clot and replaces material removed by the presentinventions rotating cutting element. The aspiration element removes bothclot elements and excess fluid to prevent the vessel from exploding.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an illustrative view of the cerebral arteries.

FIG. 2 shows an illustrative view of the cerebral arteries. (from NetterF H. The CIBA Collection of Medical Illustrations: Volumes 1, NervousSystem. Vol. 1. Part I. CIBA: USA. 1986. pp. 256).

FIG. 3 shows an illustration of a side view of one aspect of theendovascular device of the described invention.

FIG. 4 shows an illustration of a side view of one aspect of theendovascular device of the described invention.

FIG. 5A shows an illustration of a side view of one aspect of theendovascular device of the described invention.

FIG. 5B shows a top view of one embodiment of the side hole and halfloop structure of the described invention.

FIG. 5C shows a top view of one embodiment of the side hole and halfloop structure of the described invention.

FIG. 5D shows a top view of one embodiment of the side hole and halfloop structure of the described invention.

FIG. 6 shows an illustration of a side view of one embodiment of theendovascular device of the described invention.

FIG. 7A shows an illustration of a side view of one embodiment of theendovascular device of the described invention.

FIG. 7B shows an illustration of a side view of one embodiment of theendovascular device of the described invention.

FIG. 7C shows an illustration of a perspective view of one embodiment ofthe endovascular device of the described invention.

FIG. 7D shows an illustration of a cross section view of one embodimentof the endovascular device of the described invention.

FIG. 7E shows an illustration of a cross section view of one embodimentof the endovascular device of the described invention.

FIG. 7F shows an illustration of a side view of one embodiment of theendovascular device of the described invention.

FIG. 7G shows an illustration of a side view of one embodiment of theendovascular device of the described invention.

FIG. 7H shows an illustration of a side view of one embodiment of theendovascular device of the described invention.

FIG. 7I shows an illustration of a side view of one embodiment of theendovascular device of the described invention.

FIG. 7J shows an illustration of a cross section view of one embodimentof the endovascular device of the described invention.

FIG. 7K shows an illustration of a cross section view of one embodimentof the endovascular device of the described invention wherein the flareddistal end is adapted to cinch close with a lasso-type mechanism.

FIG. 8 show a cross-sectional view of one embodiment of the endovasculardevice of the described invention.

FIG. 9 illustrates a side view of the rotating, macerating andirrigating hypotube, including multiple irrigation side holes and endhole, of one embodiment of the described invention disposed within thelumen (cutaway) of a blood vessel.

FIG. 10A shows a perspective view of one embodiment of the endovasculardevice of the described invention.

FIG. 10B shows a perspective view of one embodiment of the endovasculardevice of the described invention.

FIG. 11A shows a cross section side view of one embodiment of theendovascular device of the described invention.

FIG. 11B shows a cross section side view of one embodiment of theendovascular device of the described invention.

FIG. 12A shows a cross section side view of one embodiment of theendovascular device of the described invention.

FIG. 12B shows a cross section side view of one embodiment of theendovascular device of the described invention.

FIG. 13A shows a cross section side view of one embodiment of theendovascular device of the described invention.

FIG. 13B shows a cross section side view of one embodiment of theendovascular device of the described invention.

FIG. 14 shows a cross section side view of one embodiment of a balloondisposed upon the simultaneous aspirating, irrigating, maceratingmicrocatheter of the current invention, further depicting reversal ofblood flow distal to the balloon mounted aspiration catheter.

FIG. 15 shows a cross section side view of one embodiment of thesimultaneous, irrigating, macerating microcatheter of the currentinvention inserted through the femoral vein disposed at the site of aniliac clot, further depicting a filter-tip aspiration catheter insertedinto the inferior vena cava (IVC) to simultaneously catch thrombireleased by the procedure.

FIG. 16 shows an alternative embodiment of the current invention whereinan aspiration catheter may be introduced via the descending aorta.

FIG. 17 shows an alternative embodiment of the current invention whereina filter-tipped catheter has no sheath.

FIG. 18 shows an alternative flared filter embodiment of the disclosedinvention as depicted in FIG. 7K, wherein the orientation of said filteris reversed with open ring disposed proximal to the introducingcatheter, having a drawstring-type cincture.

FIG. 19 shows an alternative flared filter embodiment of the disclosedinvention as depicted in FIG. 19, wherein the cincture is a lasso-type.

FIG. 20 shows alternative flared filter embodiment of the disclosedinvention as depicted in FIG. 19, wherein the cincture encloses the atleast one control string or wire in an array of hoops disposed about theperiphery of the rim of said flared filter.

FIG. 21A shows a cross-section (A-A) of the alternate embodiment shownin FIG. 18 of the lasso channel or lumen.

FIG. 21B shows a cross-section of a filter-tipped lasso channelincluding moveable elements.

FIG. 22 shows an alternative of the embodiment of FIG. 18, wherein theflared filter is depicted in an opposite orientation, wherein a staffwire and strut wires facilitate the closing mechanism.

FIG. 23 shows an alternative embodiment of FIG. 22, further depicting anattachment point forming a fixed-length lasso without a staff wire orstrut wires.

FIG. 24 shows an alternative embodiment of the current invention whereinopening and closing of the flared uses an additional control string orwire passing through a side hole of the lasso channel disposed at abend.

FIG. 25 shows an alternative embodiment of the current invention havinga filtered-tip affixed at the distal end of the lasso channel with afixed-loop closing mechanism.

FIG. 26 shows an alternative embodiment of FIG. 25, wherein thefixed-loop closing mechanism is replaced by a drawstring-closingmechanism.

FIG. 27 an alternative embodiment of FIG. 26, wherein the control stringor wire closing mechanism is contained by hoops instead of a peripheralchannel.

FIG. 28 shows an alternative embodiment of FIG. 26, wherein the catheteris embedded in the wall of lasso channel to form a drawstring closingmechanism.

FIG. 29 shows an alternative embodiment of FIG. 28, wherein the controlstring or wire closing mechanism is contained by hoops instead of aperipheral channel.

DETAILED DESCRIPTION OF THE INVENTION Anatomical Terms

When referring to animals that typically have one end with a head andmouth, with the opposite end often having the anus and tail, the headend is referred to as the cranial end, while the tail end is referred toas the caudal end. Within the head itself, rostral refers to thedirection toward the end of the nose, and caudal is used to refer to thetail direction. The surface or side of an animal's body that is normallyoriented upwards, away from the pull of gravity, is the dorsal side; theopposite side, typically the one closest to the ground when walking onall legs, swimming or flying, is the ventral side. On the limbs or otherappendages, a point closer to the main body is “proximal”; a pointfarther away is “distal”. Three basic reference planes are used inzoological anatomy. A “sagittal” plane divides the body into left andright portions. The “midsagittal” plane is in the midline, i.e. it wouldpass through midline structures such as the spine, and all othersagittal planes are parallel to it. A “coronal” plane divides the bodyinto dorsal and ventral portions. A “transverse” plane divides the bodyinto cranial and caudal portions.

When referring to humans, the body and its parts are always describedusing the assumption that the body is standing upright. Portions of thebody which are closer to the head end are “superior” (corresponding tocranial in animals), while those farther away are “inferior”(corresponding to caudal in animals). Objects near the front of the bodyare referred to as “anterior” (corresponding to ventral in animals);those near the rear of the body are referred to as “posterior”(corresponding to dorsal in animals). A transverse, axial, or horizontalplane is an X-Y plane, parallel to the ground, which separates thesuperior/head from the inferior/feet. A coronal or frontal plane is aY-Z plane, perpendicular to the ground, which separates the anteriorfrom the posterior. A sagittal plane is an X-Z plane, perpendicular tothe ground and to the coronal plane, which separates left from right.The midsagittal plane is the specific sagittal plane that is exactly inthe middle of the body.

Structures near the midline are called medial and those near the sidesof animals are called lateral. Therefore, medial structures are closerto the midsagittal plane, lateral structures are further from themidsagittal plane. Structures in the midline of the body are median. Forexample, the tip of a human subject's nose is in the median line.

Ipsilateral means on the same side, contralateral means on the otherside and bilateral means on both sides. Structures that are close to thecenter of the body are proximal or central, while ones more distant aredistal or peripheral. For example, the hands are at the distal end ofthe arms, while the shoulders are at the proximal ends.

The term “aneurysm”, as used herein, refers to a localized widening(dilatation) of an artery, a vein, or the heart. At the point of ananeurysm, there is typically a bulge, where the wall of the blood vesselor organ is weakened and may rupture.

Blood flow in most aneurysms is regular and predictable primarilyaccording to the geometric relationship between the aneurysm and itsparent artery. As blood flows within the parent artery with an aneurysm,divergence of blood flow, as occurs at the inlet of the aneurysm, leadsto dynamic disturbances, producing increased lateral pressure andretrograde vortices that are easily converted to turbulence. Blood flowproceeds from the parent vessel into the aneurysm at the distal ordownstream extent of the aneurysm neck (i.e., the transition from thesac to the parent artery), circulates around the periphery along theaneurysm wall from the neck to the top of the fundus (i.e., aneurysmsac) (downstream to upstream), returning in a type of “isotropic shower”along the aneurysm wall toward the neck region, and exits the closestextent of the aneurysm neck into the parent vessel (See, e.g., StrotherC. M. Neuroradiology 1994; 36: 530-536; Moulder P. V. Physiology andbiomechanics of aneurysms. In: Kerstein M D, Moulder P V, Webb W R, eds.Aneurysms. Baltimore, Md.: Williams & Wilkins; 1983:20).

As flow persists, areas of stagnation or vortices develop within acentral zone of the aneurysm. These rotating vortices, formed at theentrance to the aneurysm at each systole (i.e., ventricle contraction)and then circulated around the aneurysm, are caused by the slipstreamsor regions of recirculating flow rolling upon themselves when they enterthe aneurysm at its downstream wall during systole. The stagnant vortexzone occurs in the center and at the fundus or upper portion of theaneurysm and becomes more pronounced in larger aneurysms. It is thisstagnant zone that is believed to promote the formation of thrombi orblood clots, particularly in giant aneurysms (See, e.g., Gobin Y. P. etal. Neuroradiology 1994; 36: 530-536; Hademenos G. J. and Massoud T. F.Stroke 1997; 28: 2067-2077).

The term “abdominal aortic aneurysm” or “AAA”, as used herein refers toan aortic diameter at least one and one-half times the normal diameterat the level of the renal arteries, which is approximately 2.0 cm.Generally, a segment of abdominal aorta with a diameter of greater than3.0 cm is considered an aortic aneurysm. Aortic aneurysms constitute the14th leading cause of death in the United States. Risk factorsassociated with AAA include age, sex, ethnicity, smoking, hypertensionand atherosclerosis, among others (See, e.g., Aggarwal S. et al. ExpClin Cardiol. 2011; 16(1): 11-15; Ouriel K. et al. J Vasc Surg. 1992;15: 12-18; Silverberg E. et al. C A Cancer J Clin. 1990; 40: 9-26).

The term “arteriovenous malformation” (“AVM”), as used herein, refers toa tangle of abnormal and poorly formed blood vessels (e.g., arteries andveins) which have a higher than normal rate of bleeding compared tonormal blood vessels.

AVMs are congenital vascular lesions that occur as a result of capillarymal-development between the arterial and venous systems. Approximately0.14% of the United States population comprises an intracranial AVM thatposes a significant risk and represents a major life threat,particularly to persons under the age of 50 years. The vesselsconstituting the AVM are weak and enlarged and serve as direct shuntsfor blood flow between the high-pressure arterial system and thelow-pressure venous system, corresponding to a large pressure gradientand small vascular resistance. The abnormal low-resistance, high-flowshunting of blood within the brain AVM without an intervening capillarybed causes the fragile dilated vessels in the nidus (i.e., tangle ofblood vessels) to become structurally abnormal and fatigued, to furtherenlarge, and to rupture (See, e.g., Wilkins R. H. Neurosurgery 1985;16:421-430; Graves V. B. et al. Invest Radiol. 1990; 25: 952-960;Hademenos G. J. et al., Neurosurgery 1996; 38: 1005-1015).

The abnormal microvessels of an AVM serve as passive conduits for bloodflow from the arterial circulation directly to the venous circulation,by-passing their normal physiological function of brain tissueperfusion. The hemodynamic consequences of an AVM occur as a result oftwo interdependent circulatory mechanisms involved in the shunting ofblood between artery and vein (See, e.g., Hademenos G. J. and Massoud T.F. Stroke 1996; 27: 1072-1083).

In the normal cerebral circulation, blood flows under a highcerebrovascular resistance and high cerebral perfusion pressure.However, the presence of a brain AVM in the normal circulationintroduces a second abnormal circuit of cerebral blood flow where theblood flow is continuously shunted under a high perfusion pressurethrough the AVM, possessing a low cerebrovascular resistance and lowvenous pressure. The clinical consequence of the abnormal shunt is asignificant increase in blood returning to the heart (approximately 4 to5 times the original amount, depending on the diameter and size of theshunt), resulting in a dangerous overload of the heart and cardiacfailure. Volumetric blood flow through an AVM ranges from 200 mL/min to800 mL/min and increases according to nidus size (See, e.g., Yamada S.Neurol Res. 1993; 15: 379-383).

The abnormal shunting of blood flow by brain AVMs rapidly removes or“steals” blood from the normal cerebral circulation and substantiallyreduces the volume of blood reaching the surrounding normal braintissue. This phenomenon, known as cerebrovascular steal, depends on thesize of the AVM and is the most plausible explanation for thedevelopment of progressive neurological deficits. Cerebrovascular stealcould translate into additional neurological complications developed asa result of cerebral ischemia or stroke in neuronal territories adjacentto an AVM (See, e.g., Manchola I. F. et al. Neurosurgery 1993; 33:556-562; Hademenos G. J. and Massoud T. F. Stroke 1997; 28: 2067-2077).

The term “arterial thrombosis”, as used herein, refers to a thrombusthat develops in an artery. Depending on where the clot forms, arterialthrombosis can cause one or more of myocardial infarction, stroke, andperipheral arterial disease.

The term “aspirate” and its grammatical forms as used herein refers toremoval of a substance from a body cavity using suction.

The term “atherectomy”, as used herein, refers to a minimally invasiveendovascular surgery technique for removing atherosclerosis from bloodvessels within the body by cutting plaque from the walls of a bloodvessel.

The term “atherosclerosis” (also known as “hardening of the arteries”)as used herein refers to a pathological process in which calcified lipidor fatty deposits from flowing blood accumulate along the innermostintimal layer of a vessel wall. Atherosclerotic plaques are found almostexclusively at the outer wall of one or both daughter vessels at majorarterial bifurcations, including the carotid. Atherosclerosis and thedevelopment of arterial plaques are the products of a host ofindependent biochemical processes including the oxidation of low-densitylipoproteins, formation of fatty streaks, and the proliferation ofsmooth muscle cells. As the plaques form, the walls become thick,fibrotic, and calcified. As a result, the lumen narrows, reducing theflow of blood to the tissues supplied by the artery (See, e.g.,Hademenos G. J. and Massoud T. F. Stroke 1997; 28: 2067-2077; HademenosG. J. Am Scientist 1997; 85: 226-235; Woolf N., Davies M. J. Sci AmScience & Medicine 1994; 1: 38-47).

Atherosclerotic deposits promote the development of blood clots or theprocess of thrombosis, due in part, to flow obstruction and to highshear stresses exerted on the vessel wall by the blood. High wall shearstress mechanically damages the inner wall of the artery, initiating alesion. Low wall shear stress encourages the deposition of particles onthe artery wall, promoting the accumulation of plaque. Turbulencecomprises also been implicated in atherosclerotic disease because it canincrease the kinetic energy deposited in the vessel walls and because itcan lead to areas of stasis, or stagnant blood flow, that promoteclotting. The presence of atherosclerotic lesions introduces anirregular vessel surface, resulting in turbulent blood flow, thuscausing the dislodgment of plaques of varying size into the bloodstream.Subsequently, the dislodged plaque lodges into a vessel of smaller size,preventing further passage of blood flow (See, e.g., Hademenos G. J. andMassoud T. F. Stroke 1997; 28: 2067-2077).

The term “atresia”, as used herein, refers to the absence or abnormalnarrowing of an opening or passage in the body. For example, aorticatresia refers to a rare congenital anomaly in which the aortic orificeis absent or closed.

The term “atrial fibrillation”, as used herein, refers to an irregularand often fast heart rate which may cause symptoms such as heartpalpitations, fatigue, and shortness of breath. Atrial fibrillationweakens the cardiac wall and introduces abnormalities in thephysiological function of the heartbeat, which ultimately result inreduced systemic pressure, conditions of ischemia and stroke.

The term “blockage”, as used herein, refers to an obstruction that makesthe movement or flow of blood difficult or impossible. Non-limitingexamples of material that comprises a blockage includes cell debris,cholesterol and fatty deposits, platelets or other cell types, andemboli.

The term “brachiocephalic trunk”, also known as “innominate artery”, asused herein, refers to a major vessel that supplies the head, neck andright arm. It is the first of three main branches of the aortic arch,which originates from the upward convexity. After arising in themidline, it courses upwards to the right, crossing the trachea, andbifurcates posteriorly to the right sternoclavicular joint into theright subclavian and right common carotid arteries. It typicallymeasures 4-5 cm in length with a diameter of approximately 12 mm.

The term “brain aneurysm”, as used herein, refers to a cerebrovasculardisease that manifests as a pouching or ballooning of the vessel wall(i.e., vascular dilation). The vascular dilatation develops at adiseased site along the arterial wall into a distended sac of stressedand thinned arterial tissue. The fully developed cerebral aneurysmtypically ranges in size from a few millimeters to 15 mm but can attainsizes greater than 2.5 cm. If left untreated, the aneurysm may continueto expand until it ruptures, causing hemorrhage, severe neurologicalcomplications and deficits, and possibly death (Hademenos G. J. andMassoud T. F. Stroke 1997; 28: 2067-2077; Hademenos G. J. Phys Today1995; 48: 24-30).

The two main treatment options for a patient suffering from a brainaneurysm are (i) surgical clipping; and (ii) endovascular coiling.Surgical clipping is an intracranial procedure in which a small metallicclip is placed along the neck of the aneurysm. The clip prevents bloodfrom entering into the aneurysm sac so that it no longer poses a riskfor bleeding. The clip remains in place, causing the aneurysm to shrinkand permanently scar. Endovascular coiling is a minimally invasivetechnique in which a catheter is inserted into the femoral artery andnavigated through the blood vessels to the vessels of the brain and intothe aneurysm. Coils are then packed into the aneurysm to the point whereit arises from the blood vessel, thus preventing blood flow fromentering the aneurysm. Additional devices, such as a stent or balloon,for example, may be needed to keep the coils in place.

The term “branch”, as used herein, refers to something that extends fromor enters into a main body or source; a division or offshoot from a mainstem (e.g., blood vessels); one of the primary divisions of a bloodvessel.

The term “cerebral venous sinus thrombosis” as used herein, refers to ablood clot that forms in the brain's venous sinuses, preventing bloodfrom draining out of the brain.

The term “coarctation” or “coarctation of the aorta”, as used herein,refers to a congenital narrowing of a short section of the aorta.

The terms “compound curves” and “multi-curves” are used interchangeablyherein to refer to multiple deflection points along the length of acatheter. By way of example, two deflection points allow a catheter tobe deflected into an “S” shape or the shape of a shepherd's hook.

The term “curve diameter”, as used herein, refers to the furthestdistance a catheter moves from its straight axis as it is beingdeflected. The curve diameter does not always remain constant duringdeflection and does not necessarily indicate the location of thecatheter tip.

The term “deflection”, as used herein, refers to movement of a cathetertip independent of the rest of the catheter.

The term “deep vein thrombosis”, as used herein, refers to a blood clotin a vein deep in the body, usually in a lower leg, thigh, pelvis, orarm.

The term “dyscrasia”, as used herein, refers to an abnormal ordisordered state of the body or a bodily part. The term “blooddyscrasia”, as used herein, refers to an abnormality of blood cells orof clotting elements.

The term “embolus” (plural “emboli”), as used herein, refers to agaseous or particulate matter that acts as a traveling “clot”. A commonexample of an embolus is a platelet aggregate dislodged from anatherosclerotic lesion. The dislodged platelet aggregate is transportedby the bloodstream through the cerebrovasculature until it reaches avessel too small for further propagation. The clot remains there,clogging the vessel and preventing blood flow from entering the distalvasculature. Emboli can originate from distant sources such as theheart, lungs, and peripheral circulation, which may eventually travelwithin the cerebral blood vessels, obstructing flow and causing stroke.Other sources of emboli include atrial fibrillation and valvulardisease. The severity of stroke depends on the size of the embolus andthe location of the obstruction. The bigger the embolus and the largerthe vessel obstruction, the larger the territory of brain at risk(Hademenos G. J. and Massoud T. F. Stroke 1997; 28: 2067-2077).

The term “endoluminal”, as used herein, refers to the state of beingwithin a tubular organ or structure (e.g., blood vessel, duct,gastrointestinal tract, etc.) or within a lumen.

The term “endovascular thrombectomy” or “mechanical thrombectomy”, asused herein, refers to a procedure that physically removes a thrombusfrom a blood vessel. The procedure may involve a long catheter withsuction, rotating device, high-speed fluid jet, or ultrasound devicethat is used to physically break up and/or remove a thrombus in theblood vessel. Subgroups of this procedure include “proximal endovascularthrombectomy,” wherein suction thrombectomy devices remove occlusivematerial from the blood vessel by aspiration, and “distal endovascularthrombectomy,” wherein clot removal devices physically seize occlusivematerial and drag it out of the blood vessel (Singh P., et al.,Endovascular treatment of acute ischemic stroke, J Neurosci Rural Pract.2013 July-September; 4(3): 298-303). During proximal endovascularthrombectomy, manual suction is done by moving forward an aspirationcatheter at the proximal surface of the thrombus. Manual aspiration isthen carried out and the aspiration catheter is taken back undercontinuous negative pressure. A variation of the proximal endovascularthrombectomy method comprises a dedicated reperfusion catheter attachedto a pumping system applying constant aspiration. In contrast, in distalendovascular thrombectomy, the occlusion site comprises to be traversedwith a microcatheter so as to deploy the device beyond the thrombus. Thedevice is then pulled back into the thrombus and positioned within theclot, followed by withdrawal of the clot and the device out of thepatient's body (See. e.g., Singh P., et al., Endovascular treatment ofacute ischemic stroke, J Neurosci Rural Pract. 2013 July-September;4(3): 298-303).

The term “French” (abbreviated “Fr” or “F” or “Fg” or “Ga” or “CH” or“Ch”), as used herein, is a system used to measure the diameter of acatheter. The French unit of measure is equivalent to three times thediameter in millimeters (mm). For example, 9 Fr is equivalent to adiameter of 3 mm.

The term “hypotube” as used herein refers to a small, micro ornanoradius tube of any length with micro-engineered features along itslength.

The term “introducer”, as used herein, refers to an instrument such as atube or a sheath that is placed within a vein or artery for introductionof a flexible device, for example, a catheter, needle, wire, etc.

The terms “ischemic” and “ischemia”, as used herein, refer to deficientsupply of blood to a body part generally due to obstruction of theinflow of arterial blood (e.g., by the narrowing of arteries, spasm ordisease).

The term “lumen”, as used herein, refers to the inner open space orcavity of a tubular structure.

The term “macerate” and its other grammatical forms as used hereinrefers to causing to separate into smaller parts.

The term “myocardial infarction”, as used herein, refers to death ofcells of an area of heart muscle as a result of oxygen deprivation,which in turn is caused by obstruction of the blood supply; commonlyreferred to as a “heart attack”. The most common cause is thrombosis ofan atherosclerotic coronary artery or a spasm. Less common causesincluded coronary artery abnormalities and vasculitis (inflammation ofblood vessels).

The term “myocardial infarction with thrombus”, as used herein, refersto an acute myocardial infarction caused by rupture of anatherosclerotic plaque that initiates blood clot (thrombus) formation,which totally or partially occludes a coronary artery.

The term “percutaneous coronary intervention” (PCI), as used herein,refers to a procedure that uses a catheter to place a stent at the siteof an occlusion to open up blood vessels in the heart that have beennarrowed by plaque buildup.

The term “recanalization”, as used herein, refers to the process ofrestoring flow to or reuniting an interrupted channel of a bodily tube(e.g., a blood vessel).

The term “reperfusion”, as used herein, refers to restoration of theflow of blood to a previously ischemic organ or tissue (e.g., heart orbrain).

The term “retrievable thrombectomy stents”, as used herein, refers to aself-expandable, re-sheathable, and re-constrainable stent-likethrombectomy device. Since it can be retrieved, it does not become apermanent implant, and while being recovered, it functions as amechanical thrombectomy device. The entire removal of the devicecircumvents the drawbacks of permanent stent implantation, for examplethe requirement for double anti-platelet medication, which potentiallyadds to the risk of hemorrhagic complications and the risk of in-stentthrombosis or stenosis. Under general anesthesia, using a transfemoralapproach, a guide catheter is positioned in the proximal internalcarotid artery. A guide wire is advanced coaxially over a microcatheterwithin the blocked intracranial vessel and navigated past the thrombus.The microcatheter is then advanced over the wire through the clot, andthe guide wire is substituted for the embolectomy device. Therevascularization device is placed with the middle third of the deviceresiding within the thrombus formation. The radial force of the stentretriever is capable of instantly creating a channel by squeezing thethrombus, and of partially restore blood flow to the distal territory inthe majority of cases, producing a channel for a temporary bypass. Thedevice is usually left in place for an embedding time up to 10 minutes,permitting entrapment of the thrombus within the stent struts. Toextract the thrombus, the unfolded stent and the microcatheter areslowly dragged into the guide catheter with flow reversal by continuousaspiration (Singh P. et al. J Neurosci Rural Pract. 2013 July-September;4(3): 298-303).

The term “self-expanding stents”, as used herein, refers to acylindrical mesh that is positioned at the site of a blood vesselocclusion and expanded, thereby stretching the blood vessel wall.Self-expanding stents are manufactured at (or slightly above) thediameter of a blood vessel and are crimped and constrained to a smallerdiameter until the intended delivery site is reached. The constraint isthen removed and the stent is deployed.

The term “slant height” of a cone, as used herein, refers to the lengthmeasured along a lateral face from the base to the apex along the“center” of the face. For example, the slant height “1” of a rightcircular cone is the distance from the apex to a point on the base, andis related to the height “h” and base radius “a” by the equation:1=4{square root over (h2+a2)}.

The term “stenosis” as used herein refers to an abnormal narrowing of apassage in the body. The term “restenosis”, as used herein, refers tothe recurrence of this abnormal narrowing (e.g., of a blood vessel(e.g., artery or vein) or valve).

The term “steerability”, as used herein, refers to an ability to turn orrotate the distal end of a catheter with like-for-like movement of theproximal section or the catheter handle.

The terms “subject” or “individual” or “patient” are usedinterchangeably to refer to a member of an animal species of mammalianorigin, including but not limited to, mouse, rat, cat, goat, sheep,horse, hamster, ferret, pig, dog, guinea pig, rabbit and a primate, suchas, for example, a monkey, ape, or human.

The phrase “subject in need thereof” as used herein refers to a patientthat (i) will be treated with a device of the described invention, (ii)is receiving treatment with a device of the described invention; or(iii) comprises received treatment with a device of the describedinvention, unless the context and usage of the phrase indicatesotherwise.

The term “stroke”, “acute stroke” or “cerebrovascular accident”, as usedherein, refers to neurological signs and symptoms, usually focal andacute, which result from diseases involving blood vessels of the brain.Generally, strokes are either occlusive (due to closure of a bloodvessel) or hemorrhagic (due to bleeding from a vessel). Although mostocclusive strokes are due to atherosclerosis and thrombosis, and mosthemorrhagic strokes are associated with hypertension or aneurysms,strokes of either type may occur at any age from many causes, includingcardiac disease, trauma, infection, neoplasm, blood dyscrasia, vascularmalformation, immunological disorder, and exogenous toxins. An ischemiastroke results from a lack of blood supply and oxygen to the brain thatoccurs when reduced perfusion pressure distal to an abnormal narrowing(stenosis) of a blood vessel is not compensated by autoregulatorydilation of the resistance vessels. When ischemia is sufficiently severeand prolonged, neurons and other cellular elements die. This conditionis referred to as “cerebral infarction” (See, e.g., Hart R. G. et al.,Stroke 1990; 21:1111-1121). Although the consequences of both ischemicand hemorrhagic stroke are similar (i.e., vessel obstruction, resultantreduced blood flow to the brain, neurological deficits and possiblydeath), the biophysical and hemodynamic mechanisms behind theobstruction of blood flow are different. Biophysical mechanisms for thedevelopment of obstructions that ultimately lead to stroke can arise bysix distinct processes: atherosclerosis, embolus, thrombus, reducedsystemic pressure, hemorrhage, and vasospasm (See, e.g., Hademenos G. J.and Massoud T. F., Stroke 1997; 28: 2067-2077).

The term “taper”, as used herein, refers to a reduction of thicknesstoward one end; the gradual diminution of width or thickness in anelongated object; i.e., to become more slender toward one end.

The term “thrombectomy”, as used herein, refers to the surgical excisionof a thrombus.

The term “thrombus”, as used herein, refers to an internal physiologicalmechanism responsible for the clotting of blood. A thrombus is anaggregation of platelets and fibrin formed in response either to anatherosclerotic lesion or to vessel injury. In response to vessel ortissue injury, the blood coagulation system is activated, whichinitiates a cascade of processes, transforming prothrombin, ultimatelyresulting in a fibrin clot(Prothrombin→Thrombin→Fibrinogen→Fibrin→Fibrin Clot) (See, e.g.,Hademenos G. J. and Massoud T. F. Stroke 1997; 28: 2067-2077).

Although a host of mechanisms and causes are responsible for vesselinjury, vessel injury can occur as a result of forces (e.g., shearstresses) coupled with excess energy created by the turbulent flowexerted against the inner (intimal) lining of the vessel wall,particularly an atherosclerotic vessel wall (See, e.g., Fry D. L. CircRes. 1968; 22: 165-197; Stein P. D. and Sabbah H. N. Circ Res. 1974; 35:608-614; Mustard J. F. et al. Am J Med. 1962; 33: 621-647; Goldsmith H.L. et al. Thromb Haemost 1986; 55: 415-435).

The term “tortuosity” and other grammatical forms of the term “tortuous”is used herein to refer to a property of a tube, passage or blood vessel(e.g., an artery or a vein) being twisted, crooked or having many turns.

The term “treat” or “treating” includes abrogating, substantiallyinhibiting, slowing or reversing the progression of a disease, conditionor disorder, substantially ameliorating clinical or esthetical symptomsof a condition, substantially preventing the appearance of clinical oresthetical symptoms of a disease, condition, or disorder, and protectingfrom harmful or annoying symptoms. Treating further refers toaccomplishing one or more of the following: (a) reducing the severity ofthe disorder; (b) limiting development of symptoms characteristic of thedisorder(s) being treated; (c) limiting worsening of symptomscharacteristic of the disorder(s) being treated; (d) limiting recurrenceof the disorder(s) in patients that have previously had the disorder(s);and (e) limiting recurrence of symptoms in patients that were previouslyasymptomatic for the disorder(s).

The term “vasospasm”, as used herein, refers to the sudden constrictionof a blood vessel, reducing its diameter and flow rate. When bleedingoccurs in the subarachnoid space, the arteries in the subarachnoid spacecan become spastic with a muscular contraction, which can produce afocal constriction of sufficient severity to cause total occlusion. Thelength of time that the vessel is contracted during vasospasm variesfrom hours to days. However, regardless of the duration of vesselconstriction, reduction of blood flow induces cerebral ischemia, thoughtto be reversible within the first 6 hours and irreversible thereafter.It comprises been shown that vasospasm is maximal between 5 and 10 daysafter subarachnoid hemorrhage and can occur up to 2 weeks aftersubarachnoid hemorrhage (See, e.g., Wilkins R. H. Contemp Neurosurg.1988; 10:1-66; Hademenos G. J. and Massoud T. F. Stroke 1997; 28:2067-2077).

The term “venous thrombosis”, as used herein, refers to a thrombus thatforms within a vein. A common form of venous thrombosis is deep veinthrombosis, in which the thrombus can break off, flow toward the lungs,and become a pulmonary embolism.

In the various views of the drawings, like reference charactersdesignate like or similar parts.

FIG. 3 shows a non-limiting example of one aspect of an endovasculardevice of the described invention. According to one possibleconfiguration, FIG. 3 illustrates a side view of a microcatheter 100with side holes 110 located around the circumference of the distal end120 of the microcatheter 100. According to some embodiments, themicrocatheter 100 further comprises a front hole 140 located at a tip ofthe distal end 120 of the microcatheter and a rear hole 150 located at atip of the proximal end 130 of the microcatheter. Rear hole 150 iscapable of receiving a fluid from outside a patient's body, and each ofthe side holes 110 and the front hole 140 are capable of ejecting fluidout of the microcatheter 100 into the vasculature of a patient.

According to some embodiments, variables include, without limitation,the number of side holes, the spacing of the side holes, the proximityof the side holes to the distal end, the length over which the sideholes exist, the shape of the side holes, the diameter of the sideholes, catheter wall thickness, and internal and outer diameter of thecatheter.

According to some embodiments, the side holes 110 are evenly spacedaround the circumference of the microcatheter 100. According to someembodiments, the side holes are randomly spaced around the circumferenceof the microcatheter 100. According to some embodiments, the side holes110 are spaced in a repeating pattern around the circumference of themicrocatheter 100.

According to some embodiments, the side holes 110 are located on thedistal end 120 of the microcatheter 100 for a length of from 0.1 to 60cm. According to some embodiments, the side holes 110 are present over alength of at least 0.1 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 0.5 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 1 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 5 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 10 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 20 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 30 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 40 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 50 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.According to some embodiments, the side holes 110 are present over alength of at least 60 cm on the distal end 120 of the microcatheterwithin the last 60 cm of the distal end 120 of the microcatheter 100.

According to some embodiments, the side holes 110 are located on thelast 0.5 cm of the distal end 120 of the microcatheter 100. According tosome embodiments, the side holes 110 are located on the last 1 cm of thedistal end 120 of the microcatheter 100. According to some embodiments,the side holes 110 are located on the last 3 cm of the distal end 120 ofthe microcatheter 100. According to some embodiments, the side holes 110are located on the last 5 cm of the distal end 120 of the microcatheter100. According to some embodiments, the side holes 110 are located onthe last 10 cm of the distal end 120 of the microcatheter 100. Accordingto some embodiments, the side holes 110 are located on the last 15 cm ofthe distal end 120 of the microcatheter 100. According to someembodiments, the side holes 110 are located on the last 20 cm of thedistal end 120 of the microcatheter 100. According to some embodiments,the side holes 110 are located on the last 25 cm of the distal end 120of the microcatheter 100. According to some embodiments, the side holes110 are located on the last 30 cm of the distal end 120 of themicrocatheter 100. According to some embodiments, the side holes 110 arelocated on the last 35 cm of the distal end 120 of the microcatheter100. According to some embodiments, the side holes 110 are located onthe last 40 cm of the distal end 120 of the microcatheter 100. Accordingto some embodiments, the side holes 110 are located on the last 45 cm ofthe distal end 120 of the microcatheter 100. According to someembodiments, the side holes 110 are located on the last 50 cm of thedistal end 120 of the microcatheter 100. According to some embodiments,the side holes 110 are located on the last 55 cm of the distal end 120of the microcatheter 100. According to some embodiments, the side holes110 are located on the last 60 cm of the distal end 120 of themicrocatheter 100. According to some embodiments, the side holes 110 arelocated along greater than the last 60 cm of the distal end 120 of themicrocatheter 100.

According to some embodiments, the side holes 110 are of a circularshape. According to some embodiments, the side holes 110 are of an ovalshape. According to some embodiments, the side holes 110 are of a squareshape. According to some embodiments, the side holes 110 are of arectangular shape. In some embodiment, the side holes 110 are of atriangular shape. According to some embodiments, the side holes 110 areof a trapezoidal shape. According to some embodiments, the side holes110 are of a diamond shape. According to some embodiments, the sideholes 110 are of a pentagon shape. According to some embodiments, theside holes 110 are of a hexagon shape. According to some embodiments,the side holes 110 are of a heptagon shape. According to someembodiments, the side holes 110 are of an octagon shape. According tosome embodiments, the side holes 110 are of a nonagon shape. Accordingto some embodiments, the side holes 110 are of a decagon shape.According to some embodiments, the side holes 110 are of an irregularshape. According to some embodiments, the side holes 110 are of amixture of two or more of circular, oval, square, rectangle, triangle,diamond, pentagon, hexagon, heptagon, octagon, nonagon, decagon, andirregular shapes.

According to some embodiments, the size of the side holes 110 is greaterthan the size of the front hole 140 on the distal end 120 of themicrocatheter 100. According to some embodiments, the size of the sideholes 110 is less than the size of the front hole 140 on the distal end120 of the microcatheter 100. According to some embodiments, the size ofthe side holes 100 is approximately the same as the size of the fronthole 140 on the distal end 120 of the microcatheter 100.

According to some embodiments, the opening of a side hole 110 is at anangle relative to the opening of the front hole 140. According to someembodiments, the opening of a side hole 110 is at a 90-degree anglerelative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 10-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 20-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 30-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 40-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 50-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 60-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 70-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at an 80-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 100-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 120-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 130-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 140-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 150-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 160-degreeangle relative to the opening of the front hole. According to someembodiments, the opening of a side hole 110 is at least at a 170-degreeangle relative to the opening of the front hole. According to someembodiments, a plurality of side holes 110 is at the same angle relativeto the front hole 140. According to some embodiments, a plurality ofside holes 110 is at different angles relative to the front hole 140.

According to some embodiments, the microcatheter 100 comprises an outerdiameter between 34 French and 0.1 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 34 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 32 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 30 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 28 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 26 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 24 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 22 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 20 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 19 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 18 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 17 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 16 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 15 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 14 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 13 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 12 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 11 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 10 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 9 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 8 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 7 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 6 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 5 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 4 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 3 French. According to some embodiments, the microcatheter 100comprises an outer diameter of less than 2 French. According to someembodiments, the microcatheter 100 comprises an outer diameter of lessthan 1 French.

According to some embodiments, the side holes 110 are of a width attheir widest point of between 17 French and 0.01 French. According tosome embodiments, the side holes 110 are of a width at their widestpoint of less than 17 French. According to some embodiments, the sideholes 110 are of a width at their widest point of less than 16 French.According to some embodiments, the side holes 110 are of a width attheir widest point of less than 15 French. According to someembodiments, the side holes 110 are of a width at their widest point ofless than 14 French. According to some embodiments, the side holes 110are of a width at their widest point of less than 13 French. Accordingto some embodiments, the side hole 110 have a width at their widestpoint of less than 12 French. According to some embodiments, the sideholes 110 are of a width at their widest point of less than 11 French.According to some embodiments, the side holes 110 are of a width attheir widest point of less than 10 French. According to someembodiments, the side holes 110 are of a width at their widest point ofless than 9 French. According to some embodiments, the side holes 110are of a width at their widest point of less than 8 French. According tosome embodiments, the side holes 110 are of a width at their widestpoint of less than 7 French. According to some embodiments, the sideholes 110 are of a width at their widest point of less than 6 French.According to some embodiments, the side holes 110 are of a width attheir widest point of less than 5 French. According to some embodiments,the side holes 110 are of a width at their widest point of less than 4French. According to some embodiments, the side holes 110 are of a widthat their widest point of less than 3 French. According to someembodiments, the side holes 110 are of a width at their widest point ofless than 2 French. According to some embodiments, the side holes 110are of a width at their widest point of less than 1 French. According tosome embodiments, the side holes 110 are of a width at their widestpoint of less than 0.1 French. According to some embodiments, the sideholes 110 are of a width at their widest point of less than 0.01 French.

According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter between 32 French and 0.1 French.According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter of less than 32 French. According tosome embodiments, the luminal space defined by the microcatheter 100 isof a diameter of less than 30 French. According to some embodiments, theluminal space defined by the microcatheter 100 is of a diameter of lessthan 28 French. According to some embodiments, the luminal space definedby the microcatheter 100 is of a diameter of less than 26 French.According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter of less than 24 French. According tosome embodiments, the luminal space defined by the microcatheter 100 isof a diameter of less than 22 French. According to some embodiments, theluminal space defined by the microcatheter 100 is of a diameter of lessthan 20 French. According to some embodiments, the luminal space definedby the microcatheter 100 is of a diameter of less than 19 French.According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter of less than 18 French. According tosome embodiments, the luminal space defined by the microcatheter 100 isof a diameter of less than 17 French. According to some embodiments, theluminal space defined by the microcatheter 100 is of a diameter of lessthan 16 French. According to some embodiments, the luminal space definedby the microcatheter 100 is of a diameter of less than 15 French.According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter of less than 14 French. According tosome embodiments, the luminal space defined by the microcatheter 100 isof a diameter of less than 13 French. According to some embodiments, theluminal space defined by the microcatheter 100 is of a diameter of lessthan 12 French. According to some embodiments, the luminal space definedby the microcatheter 100 is of a diameter of less than 11 French.According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter of less than 10 French. According tosome embodiments, the luminal space defined by the microcatheter 100 isof a diameter of less than 9 French. According to some embodiments, theluminal space defined by the microcatheter 100 is of a diameter of lessthan 8 French. According to some embodiments, the luminal space definedby the microcatheter 100 is of a diameter of less than 7 French.According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter of less than 6 French. According tosome embodiments, the luminal space defined by the microcatheter 100 isof a diameter of less than 5 French. According to some embodiments, theluminal space defined by the microcatheter 100 is of a diameter of lessthan 4 French. According to some embodiments, the luminal space definedby the microcatheter 100 is of a diameter of less than 3 French.According to some embodiments, the luminal space defined by themicrocatheter 100 is of a diameter of less than 2 French. According tosome embodiments, the luminal space defined by the microcatheter 100 isof a diameter of less than 1 French. According to some embodiments, theluminal space defined by the microcatheter 100 is of a diameter of lessthan 0.1 French. According to some embodiments, the luminal spacedefined by the microcatheter 100 is of a diameter of less than 0.01French.

According to some embodiments, the microcatheter 100 is made from one ormore of the following materials: silicone, polyurethane, polyethylene,polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), latex,and thermoplastic elastomers. According to some embodiments, themicrocatheter 100 comprises an inner layer made of a first material, andan outer layer made from a second material. According to someembodiments, the microcatheter is reinforced with steel or othersuitable material.

According to some embodiments, the microcatheter 100 is made of amaterial and is of dimensions able to withstand internal pressurebetween 0.1 and 1200 psi. According to some embodiments, themicrocatheter 100 is able to withstand internal pressures greater than0.1 psi. According to some embodiments, the microcatheter 100 is able towithstand internal pressures greater than 1 psi. According to someembodiments, the microcatheter 100 is able to withstand internalpressures greater than 5 psi. According to some embodiments, themicrocatheter 100 is able to withstand internal pressures greater than10 psi. According to some embodiments, the microcatheter 100 is able towithstand internal pressures greater than 20 psi. According to someembodiments, the microcatheter 100 is able to withstand internalpressures greater than 40 psi. According to some embodiments, themicrocatheter 100 is able to withstand internal pressures greater than80 psi. According to some embodiments, the microcatheter 100 is able towithstand internal pressures greater than 160 psi. According to someembodiments, the microcatheter 100 is able to withstand internalpressures greater than 320 psi. According to some embodiments, themicrocatheter 100 is able to withstand internal pressures greater than460 psi. According to some embodiments, the microcatheter 100 is able towithstand internal pressures greater than 920 psi. According to someembodiments, the microcatheter 100 is able to withstand internalpressures greater than 1000 psi. According to some embodiments, themicrocatheter 100 is able to withstand internal pressures greater than1200 psi.

According to some embodiments, the material allows for a variablepressure between the proximal end and the distal end. According to someembodiments, the microcatheter is able to withstand a greater pressureat the proximal end and a lesser pressure at the distal end. Accordingto some embodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 1.5:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 2:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 3:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 4:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 5:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 6:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 7:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 8:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 9:1. According to someembodiments, the pressure the microcatheter can withstand at theproximal end is greater than the pressure the microcatheter canwithstand at the proximal end by a ratio of 10:1.[0224] According tosome embodiments, the outer diameter of the microcatheter 100 at theproximal end 130 is approximately the same as the outer diameter of themicrocatheter 100 at the distal end 120. According to some embodiments,the outer diameter of the microcatheter 100 at the proximal end 130 isgreater than the outer diameter of the microcatheter 100 at the distalend 120. According to some embodiments, the outer diameter of themicrocatheter 100 at the proximal end 130 is less than the outerdiameter of the microcatheter 100 at the distal end 120. According tosome embodiments, the outer diameter of the microcatheter 100 variesalong the length of the microcatheter.

According to some embodiments, the inner luminal diameter of themicrocatheter 100 at the proximal end 130 is approximately the same asthe inner luminal diameter of the microcatheter 100 at the distal end120. According to some embodiments, the inner luminal diameter of themicrocatheter 100 at the proximal end 130 is greater than the innerluminal diameter of the microcatheter 100 at the distal end 120.According to some embodiments, the inner luminal diameter ofmicrocatheter 100 at the proximal end 130 is less than the inner luminaldiameter of the microcatheter 100 at the distal end 120.

According to some embodiments, the diameter of the microcatheter isadapted to provide fluid proximal, distal, or inside the site of anocclusion. According to some embodiments, the microcatheter 100 can beused to irrigate a blood vessel on the distal side of a thrombus, on aproximal side of a thrombus, or both. By way of non-limiting example,according to some embodiments the microcatheter 100 can be pushedthrough a thrombus in a proximal to distal direction. According to someembodiments, the microcatheter 100 can be used in conjunction with anaspirator to perform a direct aspiration first pass technique (ADAPT) toirrigate at and distal to a thrombus to prevent the creation of an emptyvacuum distal to the thrombus. According to some such embodiments, thethrombus then is aspirated proximally so the catheter can pick up theclot.

According to some embodiments, the diameter of the microcatheter isadapted to provide fibrinolytics to the site of an occlusion. Accordingto some embodiments, the microcatheter is adapted to provide fluid,fluid including saline solution, HEP-saline, neuro-protective cooledsolution, and other neuro-protective liquids, proximal, distal, orinside the site of an occlusion. According to some embodiments, thediameter of the microcatheter is adapted to provide fluid while notobstructing suction of an aspirator.

FIG. 4 shows an exemplary and non-limiting example of one aspect of theendovascular device of the described invention that includes maceratingloops mounted on the microwire.

According to some embodiments, a macerating microwire 200 comprises acentral wire 250 comprising a proximal end 210 and a distal end 220.Attached to the distal end of the microwire are one or more half-loopstructures 230. According to some embodiments, the half loop-structures230 comprise a second microwire with a first end and a second end,wherein both the first end and second end of the half-loop structure areattached to the central wire 250 of the macerating microwire, and crossstrut wires 240 are connected to both the second microwire of thehalf-loop structure and the central wire 250 of the maceratingmicrowire. Said cross-strut wires 240 may vary in size but are limitedby the maximum interior radius of the vessel.

According to some embodiments, variables include, without limitation,the diameter of the central wire, size of the half loops, placement ofthe half loops, and construction of the half loops.

According to some embodiments, the proximal end 210 of the microwire 200can be connected to a power-driven plug that rotates the maceratingmicrowire 200 around the axis of the central wire 250. For example, thepower-driven plug can be battery or electrically powered.

According to some embodiments, the diameter of the central wire 250 isbetween 0.1 inches and 0.001 inches. According to some embodiments, thediameter of the central wire 250 is between 0.09 and 0.002 inches.According to some embodiments, the diameter of the central wire 250 isbetween 0.08 and 0.003 inches. According to some embodiments, thediameter of the central wire 250 is between 0.07 and 0.004 inches.According to some embodiments, the diameter of the central wire 250 isbetween 0.06 and 0.005 inches. According to some embodiments, thediameter of the central wire 250 is between 0.05 and 0.006 inches.According to some embodiments, the diameter of the central wire 250 isbetween 0.04 and 0.007 inches. According to some embodiments, thediameter of the central wire 250 is between 0.03 and 0.008 inches.According to some embodiments, the diameter of the central wire 250 isbetween 0.02 and 0.009 inches. According to some embodiments, thediameter of the central wire 250 is between 0.01 and 0.009 inches.

According to some embodiments, the diameter of the central wire 250 isgreater than 0.001 inches. According to some embodiments, the diameterof the central wire 250 is greater than 0.002 inches. According to someembodiments, the diameter of the central wire 250 is greater than 0.003inches. According to some embodiments, the diameter of the central wire250 is greater than 0.004 inches. According to some embodiments, thediameter of the central wire 250 is greater than 0.005 inches. Accordingto some embodiments, the diameter of the central wire 250 is greaterthan 0.006 inches. According to some embodiments, the diameter of thecentral wire 250 is greater than 0.007 inches. According to someembodiments, the diameter of the central wire 250 is greater than 0.008inches. According to some embodiments, the diameter of the central wire250 is greater than 0.009 inches. According to some embodiments, thediameter of the central wire 250 is greater than 0.01 inches. Accordingto some embodiments, the diameter of the central wire 250 is greaterthan 0.02 inches. According to some embodiments, the diameter of thecentral wire 250 is greater than 0.03 inches. According to someembodiments, the diameter of the central wire 250 is greater than 0.04inches. According to some embodiments, the diameter of the central wire250 is greater than 0.05 inches. According to some embodiments, thediameter of the central wire 250 is greater than 0.06 inches. Accordingto some embodiments, the diameter of the central wire 250 is greaterthan 0.07 inches. According to some embodiments, the diameter of thecentral wire 250 is greater than 0.08 inches. According to someembodiments, the diameter of the central wire 250 is greater than 0.09inches.

According to some embodiments, the diameter of the central wire 250 isless than 0.1 inches. According to some embodiments, the diameter of thecentral wire 250 is less than 0.05 inches. According to someembodiments, the diameter of the central wire 250 is less than 0.04inches. According to some embodiments, the diameter of the central wire250 is less than 0.03 inches. According to some embodiments, thediameter of the central wire 250 is less than 0.02 inches. According tosome embodiments, the diameter of the central wire 250 is less than 0.01inches. According to some embodiments, the diameter of the central wire250 is less than 0.009 inches. According to some embodiments, thediameter of the central wire 250 is less than 0.008 inches. According tosome embodiments, the diameter of the central wire 250 is less than0.007 inches. According to some embodiments, the diameter of the centralwire 250 is less than 0.006 inches. According to some embodiments, thediameter of the central wire 250 is less than 0.005 inches. According tosome embodiments, the diameter of the central wire 250 is less than0.004 inches. According to some embodiments, the diameter of the centralwire 250 is less than 0.003 inches. According to some embodiments, thediameter of the central wire 250 is less than 0.002 inches. According tosome embodiments, the diameter of the central wire 250 is less than0.001 inches.

According to some embodiments, the diameter of the central wire 250 is0.1 inches. According to some embodiments, the diameter of the centralwire 250 is 0.05 inches. According to some embodiments, the diameter ofthe central wire 250 is 0.04 inches. According to some embodiments, thediameter of the central wire 250 is 0.03 inches. According to someembodiments, the diameter of the central wire 250 is 0.02 inches.According to some embodiments, the diameter of the central wire 250 is0.01 inches. According to some embodiments, the diameter of the centralwire 250 is 0.009 inches. According to some embodiments, the diameter ofthe central wire 250 is 0.008 inches. According to some embodiments, thediameter of the central wire 250 is 0.007 inches. According to someembodiments, the diameter of the central wire 250 is 0.006 inches.According to some embodiments, the diameter of the central wire 250 is0.005 inches. According to some embodiments, the diameter of the centralwire 250 is 0.004 inches. According to some embodiments, the diameter ofthe central wire 250 is 0.003 inches. According to some embodiments, thediameter of the central wire 250 is 0.002 inches. According to someembodiments, the diameter of the central wire 250 is 0.001 inches.

According to some embodiments, the central wire 250 terminates at thedistal end 220 with a soft wire tip. According to some embodiments, thecentral wire 250 terminates at the distal end 220 with a soft roundmetal atraumatic ball tip.

According to some embodiments, the half loops 230 are comprised of wireof the same diameter as the central wire 250. According to someembodiments, the half loops 230 comprise a wire of a smaller diameterthan the diameter of the central wire 250. According to someembodiments, the half loops 230 comprise a wire of a larger diameterthan the diameter of the central wire 250. According to someembodiments, the diameter of the wire comprising the half loops 230 isof a diameter between 0.1 inches and 0.006 inches. According to someembodiments, the diameter of the wire comprising the half loops 230 isof a diameter between 0.006 inches and 0.008 inches. According to someembodiments, the diameter of the wire comprising the half loops 230 isless than 0.1 inches. According to some embodiments, the diameter of thewire comprising the half loops 230 is less than 0.05 inches. Accordingto some embodiments, the diameter of the wire comprising the half loops230 is less than 0.04 inches. According to some embodiments, thediameter of the wire comprising the half loops 230 is less than 0.03inches. According to some embodiments, the diameter of the wirecomprising the half loops 230 is less than 0.02 inches. According tosome embodiments, the diameter of the wire comprising the half loops 230is less than 0.01 inches. According to some embodiments, the diameter ofthe wire comprising the half loops 230 is less than 0.009 inches.According to some embodiments, the diameter of the wire comprising thehalf loops 230 is less than 0.008 inches. According to some embodiments,the diameter of the wire comprising the half loops 230 is less than0.007 inches. According to some embodiments, the diameter of the wirecomprising the half loops 230 is less than 0.006 inches. According tosome embodiments, the diameter of the wire comprising the half loops 230is less than 0.005 inches. According to some embodiments, the diameterof the wire comprising the half loops 230 is less than 0.004 inches.According to some embodiments, the diameter of the wire comprising thehalf loops 230 is less than 0.003 inches. According to some embodiments,the diameter of the wire comprising the half loops 230 is less than0.002 inches. According to some embodiments, the diameter of the wirecomprising the half loops 230 is less than 0.001 inches.

According to some embodiments, one or more half loop 230 is connected tothe central wire 250 around the circumference of the central wire 250.According to some embodiments, the circumference of the central wirecomprises half loops 230 placed every 10 degrees of rotation around thecentral wire 250. According to some embodiments the circumference of thecentral wire comprises half loops 230 placed every 20 degrees ofrotation around the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 30 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 40 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 50 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 60 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 70 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 80 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 90 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 100 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 110 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 120 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 130 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 140 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 150 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 160 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 170 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 180 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 190 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 200 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 210 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 220 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 230 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 240 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 250 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half-loops 230 placed every 260 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 270 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 280 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 290 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 300 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 310 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 320 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 330 degrees of rotation around the central wire 250. According tosome embodiments the circumference of the central wire 250 compriseshalf loops 230 placed every 340 degrees of rotation around the centralwire 250. According to some embodiments the circumference of the centralwire 250 comprises half loops 230 placed every 350 degrees of rotationaround the central wire 250. According to some embodiments thecircumference of the central wire 250 comprises half loops 230 placedevery 360 degrees of rotation around the central wire 250.

According to some embodiments, the half loops 230 are staggered so thateach half loop at least partially overlaps with at least one other halfloop 230. For example, as depicted in FIG. 4 the half loops arepositioned around the circumference of the central wire 250 every 180degrees and are staggered so that each half loop 230 overlaps with boththe preceding and the following half loop 230. In the non-limitingembodiment depicted in FIG. 4, about 33% of a preceding half loop 230overlaps with a following half loop 230. According to some embodiments,the half loops 230 are staggered around the circumference of the centralwire so that less than 10% of a preceding half loop 230 overlaps with afollowing half loop 230. According to some embodiments, the half loops230 are staggered around the circumference of the central wire so thatless than 15% of a preceding half loop 230 overlaps with a followinghalf loop 230. According to some embodiments, the half loops 230 arestaggered around the circumference of the central wire so that less than20% of a preceding half loop 230 overlaps with a following half loop230. According to some embodiments, the half loops 230 are staggeredaround the circumference of the central wire so that less than 25% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 30% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 35% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 40% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 45% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 50% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 55% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 60% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 65% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 70% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 75% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 80% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 85% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 90% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 95% of apreceding half loop 230 overlaps with a following half loop 230.According to some embodiments, the half loops 230 are staggered aroundthe circumference of the central wire so that less than 100% of apreceding half loop 230 overlaps with a following half loop 230.

According to some embodiments, the half loops can be staggered aroundthe circumference of the central wire 250 so that a preceding half loopdoes not overlap with a following half loop.

According to some embodiments, the half loop 230 comprises cross struts240 that are connected to the central wire 250 at a 90-degree anglerelative to the central wire. According to some embodiments, the crossstruts 240 are connected to the central wire at less than a 90-degreeangle. According to some embodiments, the cross struts 240 are connectedto the central wire at less than an 85-degree angle. According to someembodiments, the cross struts 240 are connected to the central wire atless than an 80-degree angle. According to some embodiments, the crossstruts 240 are connected to the central wire at less than a 75-degreeangle. According to some embodiments, the cross struts 240 are connectedto the central wire at less than a 70-degree angle. According to someembodiments, the cross struts 240 are connected to the central wire atless than a 65-degree angle. According to some embodiments, the crossstruts 240 are connected to the central wire at less than a 60-degreeangle. According to some embodiments, the cross struts 240 are connectedto the central wire at less than a 55-degree angle. According to someembodiments, the cross struts 240 are connected to the central wire atless than a 50-degree angle. According to some embodiments, the crossstruts 240 are connected to the central wire at less than a 45-degreeangle. According to some embodiments, the cross struts 240 are connectedto the central wire at less than a 40-degree angle. According to someembodiments, the cross struts 240 are connected to the central wire atless than a 35-degree angle. According to some embodiments, the crossstruts 240 are connected to the central wire at less than a 30-degreeangle. According to some embodiments, the cross struts 240 are connectedto the central wire at less than a 25-degree angle. According to someembodiments, the cross struts 240 are connected to the central wire atless than a 20-degree angle. According to some embodiments, the crossstruts 240 are connected to the central wire at less than a 15-degreeangle. According to some embodiments, the cross struts 240 are connectedto the central wire at less than a 10-degree angle. According to someembodiments, the cross struts 240 are connected to the central wire atless than a 5-degree angle.

According to some embodiments, the half loop structures 230 are made ofa flexible material that is less stiff than the central wire 250.According to some embodiments, the half loop structures 230 comprise aflexible and resilient material that allows the half loop 230 to bendand spring back to its original shape.

According to some embodiments, the microwire 200 is effective tomacerate a thrombus by contacting the thrombus with the distal end 220of the microwire 200. According to some embodiments, the microwire 200is effective to macerate a thrombus by rotating the half loops 230 whilein contact with the thrombus. According to some embodiments, themicrowire 200 can be used in conjunction with an aspirator to remove athrombus.

The embodiment shown in FIGS. 5A through 5D includes side holes forinfusion or irrigation and macerating loops mounted on a hypotube thatcan rotate for the loops to macerate a clot.

FIG. 5A, which shows an exemplary and non-limiting example of one aspectof the endovascular device of the described invention, illustrates aside view of one embodiment of the macerating irrigation catheter 300 ofthe described invention, comprising a central tube 390 having a proximalend 310 and a distal end 320. According to some embodiments, the centraltube 390 comprises side holes 330 located around the circumference ofthe distal end 320 of the central tube 390. According to someembodiments, the macerating irrigation microcatheter further comprises afront hole 340 located at the tip of the distal end 320 of themacerating irrigation microcatheter, and a rear hole 350 located at thetip of the proximal end 310 of the macerating irrigation microcatheter.The rear hole 350 is capable of receiving a fluid from outside apatient's body, and each of the side holes 330 and front hole 340 arecapable of ejecting fluid out of the central tube 390 into thevasculature of a patient. In some embodiments the fluid can be sometimesinjected into the proximal hole 350 using a power injector. In someembodiments there is a Luer Lock on the proximal end of the hypotube, at350. In some embodiment there is a soft atraumatic wire extending beyondend hole 340, and attached to it, which can have a straight, curved,ball-tip, or other shape, to facilitate the ability to advance thedevice distally when desired.

According to some embodiments, variables include, without limitation,the number of side holes, the spacing of the side holes, the proximityof the side holes to the distal end, the length over which the sideholes exist, the shape of the side holes, the diameter of the sideholes, catheter wall thickness, and internal and outer diameter of thecatheter.

According to some embodiments, the side holes of the maceratingirrigation microcatheter 300 are evenly spaced around the circumferenceof the macerating irrigation microcatheter 300. According to someembodiments, the side holes 330 are randomly spaced around thecircumference of the macerating irrigation microcatheter 300. Accordingto some embodiments, the side holes 330 are spaced in a repeatingpattern around the circumference of the macerating irrigationmicrocatheter 300.

According to some embodiments, the side holes 330 are located on thedistal end of the central tube 390 of the macerating irrigationmicrocatheter 300 for a length of 0.5 to 60 cm. According to someembodiments, the side holes 330 are located on the last 1 cm of thedistal end 320 of the central tube 390. According to some embodiments,the side holes 330 are located on the last 3 cm of the distal end 320 ofthe central tube 390. According to some embodiments, the side holes 330are located on the last 5 cm of the distal end 320 of the central tube390. According to some embodiments, the side holes 330 are located onthe last 10 cm of the distal end 320 of the central tube 390. Accordingto some embodiments, the side holes 330 are located on the last 15 cm ofthe distal end 320 of the central tube 390. According to someembodiments, the side holes 330 are located on the last 20 cm of thedistal end 320 of the central tube 390. According to some embodiments,the side holes 330 are located on the last 25 cm of the distal end 320of the central tube 390. According to some embodiments, the side holes330 are located on the last 30 cm of the distal end 320 of the centraltube 390. According to some embodiments, the side holes 330 are locatedon the last 35 cm of the distal end 320 of the central tube 390.According to some embodiments, the side holes 330 are located on thelast 40 cm of the distal end 320 of the central tube 390. According tosome embodiments, the side holes 330 are located on the last 45 cm ofthe distal end 320 of the central tube 390. According to someembodiments, the side holes 330 are located on the last 50 cm of thedistal end 320 of the central tube 390. According to some embodiments,the side holes 330 are located on the last 55 cm of the distal end 320of the central tube 390. According to some embodiments, the side holes330 are located on the last 60 cm of the distal end 320 of the centraltube 390.

With reference to FIG. 9, according to some embodiments the hypotube390, also referred to as tube 390, itself has a sinusoidal or othergeometric shape, so that the hypotube itself can effect maceration ofthe clot when it is rotated. This is a similar rotational macerationcreated by the ArgonCleaner XT. But whereas their device only allowsirrigation proximal to the clot, our device replaces the maceratingsinusoidal cable with a hypotube, thereby allowing irrigation proximalto the clot, across the length of the clot, as well as distal to theclot. Our devices are further distinguished from The Argon device byadditionally using aspiration, to prevent emboli and subsequentsecondary ischemic injury to healthy downstream tissue, eitherimmediately proximal to the clot with flow reversal techniques in mostarterial application, or distal to the thrombectomy site in most venousapplications. In many venous and some arterial applications, theprotection from emboli afforded by the aspiration is further abetted byan attached semipermeable filter (FIGS. 7G, 10A, 11A, 12A, 13A).

According to some embodiments, the side holes 330 are of a circularshape. According to some embodiments, the side holes 330 are of an ovalshape. According to some embodiments, the side holes 330 are of a squareshape. According to some embodiments, the side holes 330 are of arectangular shape. According to some embodiments, the side holes 330 areof a triangular shape. According to some embodiments, the side holes 330are of a trapezoid shape. According to some embodiments, the side holes330 are of a diamond shape. According to some embodiments, the sideholes 330 are of a pentagon shape. According to some embodiments, theside holes 330 are of a hexagon shape. According to some embodiments,the side holes 330 are of a heptagon shape. According to someembodiments, the side holes 330 are of an octagon shape. According tosome embodiments, the side holes 330 are of a nonagon shape. Accordingto some embodiments, the side holes 330 are of a decagon shape.According to some embodiments, the side holes 330 are of an irregularshape. According to some embodiments, the side holes 330 are of amixture of two or more of circular, oval, square, rectangle, triangle,diamond, pentagon, hexagon, heptagon, octagon, nonagon, decagon, andirregular shapes.

According to some embodiments, the size of the side holes 330 is greaterthan the size of the front hole 340. According to some embodiments, thesize of the side holes 330 is less than the size of the front hole 340.According to some embodiments, the size of the side holes 330 isapproximately the same size as the front hole 340.

According to some embodiments, the outer diameter of the central tube390 of the macerating irrigation microcatheter 300 is between 34 Frenchand 0.1 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 34 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 32 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 30 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 28 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 26 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 24 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 22 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 20 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 19 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 18 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 17 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 16 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 15 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 14 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 13 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 12 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 11 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 10 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 9 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 8 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 7 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 6 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 5 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 4 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 3 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 2 French. According to some embodiments, the outer diameter of thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 1 French.

According to some embodiments, the width of the side holes 330 at theirwidest point is between 17 French and 0.01 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 17 French. According to some embodiments, the width of side holes330 at their widest point is less than 16 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 15 French. According to some embodiments, the width of side holes330 at their widest point is less than 14 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 13 French. According to some embodiments, the width of side holes330 at their widest point is less than 12 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 11 French. According to some embodiments, the width of side holes330 at their widest point is less than 10 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 9 French. According to some embodiments, the width of side holes330 at their widest point is less than 8 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 7 French. According to some embodiments, the width of side holes330 at their widest point is less than 6 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 5 French. According to some embodiments, the width of side holes330 at their widest point is less than 4 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 3 French. According to some embodiments, the width of side holes330 at their widest point is less than 2 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 1 French. According to some embodiments, the width of side holes330 at their widest point is less than 0.1 French. According to someembodiments, the width of side holes 330 at their widest point is lessthan 0.01 French.

According to some embodiments, the diameter of the luminal space definedby the central tube 390 of the macerating irrigation microcatheter 300is between 32 French and 0.1 French. According to some embodiments, thediameter of the luminal space defined by the central tube 390 of themacerating irrigation microcatheter 300 is less than 32 French.According to some embodiments, the diameter of the luminal space definedby the central tube 390 of the macerating irrigation microcatheter 300is less than 30 French. According to some embodiments, the diameter ofthe luminal space defined by the central tube 390 of the maceratingirrigation microcatheter 300 is less than 28 French. According to someembodiments, the diameter of the luminal space defined by the centraltube 390 of the macerating irrigation microcatheter 300 is less than 26French. According to some embodiments, the diameter of the luminal spacedefined by the central tube 390 of the macerating irrigationmicrocatheter 300 is less than 24 French. According to some embodiments,the diameter of the luminal space defined by the central tube 390 of themacerating irrigation microcatheter 300 is less than 22 French.According to some embodiments, the diameter of the luminal space definedby the central tube 390 of the macerating irrigation microcatheter 300is less than 20 French. According to some embodiments, the diameter ofthe luminal space defined by the central tube 390 of the maceratingirrigation microcatheter 300 is less than 19 French. According to someembodiments, the diameter of the luminal space defined by the centraltube 390 of the macerating irrigation microcatheter 300 is less than 18French. According to some embodiments, the diameter of the luminal spacedefined by the central tube 390 of the macerating irrigationmicrocatheter 300 is less than 17 French. According to some embodiments,the diameter of the luminal space defined by the central tube 390 of themacerating irrigation microcatheter 300 is less than 16 French.According to some embodiments, the diameter of the luminal space definedby the central tube 390 of the macerating irrigation microcatheter 300is less than 15 French. According to some embodiments, the diameter ofthe luminal space defined by the central tube 390 of the maceratingirrigation microcatheter 300 is less than 14 French. According to someembodiments, the diameter of the luminal space defined by the centraltube 390 of the macerating irrigation microcatheter 300 is less than 13French. According to some embodiments, the diameter of the luminal spacedefined by the central tube 390 of the macerating irrigationmicrocatheter 300 is less than 12 French. According to some embodiments,the diameter of the luminal space defined by the central tube 390 of themacerating irrigation microcatheter 300 is less than 11 French.According to some embodiments, the diameter of the luminal space definedby the central tube 390 of the macerating irrigation microcatheter 300is less than 10 French. According to some embodiments, the diameter ofthe luminal space defined by the central tube 390 of the maceratingirrigation microcatheter 300 is less than 9 French. According to someembodiments, the diameter of the luminal space defined by the centraltube 390 of the macerating irrigation microcatheter 300 is less than 8French. According to some embodiments, the diameter of the luminal spacedefined by the central tube 390 of the macerating irrigationmicrocatheter 300 is less than 7 French. According to some embodiments,the diameter of the luminal space defined by the central tube 390 of themacerating irrigation microcatheter 300 is less than 6 French. Accordingto some embodiments, the diameter of the luminal space defined by thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 5 French. According to some embodiments, the diameter of theluminal space defined by the central tube 390 of the maceratingirrigation microcatheter 300 is less than 4 French. According to someembodiments, the diameter of the luminal space defined by the centraltube 390 of the macerating irrigation microcatheter 300 is less than 3French. According to some embodiments, the diameter of the luminal spacedefined by the central tube 390 of the macerating irrigationmicrocatheter 300 is less than 2 French. According to some embodiments,the diameter of the luminal space defined by the central tube 390 of themacerating irrigation microcatheter 300 is less than 1 French. Accordingto some embodiments, the diameter of the luminal space defined by thecentral tube 390 of the macerating irrigation microcatheter 300 is lessthan 0.1 French. According to some embodiments, the diameter of theluminal space defined by the central tube 390 of the maceratingirrigation microcatheter 300 is less than 0.01 French.

According to some embodiments, the central tube 390 of the maceratingirrigation microcatheter 300 is made from one or more of the followingmaterials: silicone, polyurethane, polyethylene, polytetrafluoroethylene(PTFE), polyethylene terephthalate (PET), latex, and thermoplasticelastomers. According to some embodiments, the central tube 390 of themacerating irrigation microcatheter 300 comprises an inner layer made ofa first material, and an outer layer made from a second material.According to some embodiments, the central tube 390 of the maceratingirrigation microcatheter 300 is reinforced with steel or other suitablematerial.

According to some embodiments, the central tube 390 of the maceratingirrigation microcatheter 300 is made of a material and of dimensionsable to withstand internal pressure between 0.1 and 1200 psi. Accordingto some embodiments, the central tube 390 is able to withstand internalpressures greater than 0.1 psi. According to some embodiments, thecentral tube 390 is able to withstand internal pressures greater than 1psi. According to some embodiments, the central tube 390 is able towithstand internal pressures greater than 5 psi. According to someembodiments, the central tube 390 is able to withstand internalpressures greater than 10 psi. According to some embodiments, thecentral tube 390 is able to withstand internal pressures greater than 15psi. According to some embodiments, the central tube 390 is able towithstand internal pressures greater than 20 psi. According to someembodiments, the central tube 390 is able to withstand internalpressures greater than 40 psi. According to some embodiments, thecentral tube 390 is able to withstand internal pressures greater than 80psi. According to some embodiments, the central tube 390 is able towithstand internal pressures greater than 160 psi. According to someembodiments, the central tube 390 is able to withstand internalpressures greater than 320 psi. According to some embodiments, thecentral tube 390 is able to withstand internal pressures greater than460 psi. According to some embodiments, the central tube 390 is able towithstand internal pressures greater than 920 psi. According to someembodiments, the central tube 390 is able to withstand internalpressures greater than 1000 psi. According to some embodiments, thecentral tube 390 is able to withstand internal pressures greater than1200 psi.

According to some embodiments, the outer diameter of the central tube390 at the proximal end 310 is approximately the same as the outerdiameter of the central tube 390 at the distal end 320. According tosome embodiments, the outer diameter of the central tube 390 at theproximal end 310 is greater than the outer diameter of the central tube390 at the distal end 320. According to some embodiments, the outerdiameter of the central tube 390 at the proximal end 310 is less thanthe outer diameter of the central tube 390 at the distal end 320.According to some embodiments, the outer diameter of the central tube390 varies along its length.

According to some embodiments, the inner luminal diameter of the centraltube 390 at the proximal end 310 is approximately the same as the innerluminal diameter of the central tube 390 at the distal end 320.According to some embodiments, the inner luminal diameter of the centraltube 390 at the proximal end 310 is greater than the inner luminaldiameter of the central tube 390 at the distal end 320. According tosome embodiments, the inner luminal diameter of the central tube 390 atthe proximal end 310 is less than the inner luminal diameter of thecentral tube 390 at the distal end 320. According to some embodiments,the inner luminal diameter of the central tube 390 varies along itslength.

According to some embodiments, the macerating irrigation microcatheter300 further comprises one or more half loop structures 360. Asillustrated in FIG. 5A, according to some embodiments, one or more halfloop structures 360 are attached to the distal end 320 of the centraltube 390. According to some embodiments, the half loop structures 360comprise a microwire 370 comprising a first end and a second end,wherein both the first end and the second end are connected to theoutside of the central tube 390. According to some embodiments, the halfloop structures 360 comprise cross strut wires 380 connected to both themicrowire 370 and the central tube 390. Said cross-strut wires 380 mayvary in size but are limited by the maximum interior radius of thevessel.

According to some embodiments, variables include, without limitation,the diameter of the microwire, size of the half loops, placement of themacerating half loops, and construction of the macerating half loops.

According to some embodiments, the proximal end 310 of the central tube390 can be connected to a power-driven plug that rotates the maceratingirrigation microcatheter 300 around its central axis. According to somesuch embodiments, the power-driven plug may be battery or electricallypowered.

According to some embodiments, the half loops 360 are comprised of wireof a diameter between 0.1 inches and 0.006 inches. According to someembodiments, the half loops 360 are comprised of wire of a diameter ofless than 0.1 inches. According to some embodiments, the half loops 360are comprised of wire of a diameter of less than 0.05 inches. Accordingto some embodiments, the half loops 360 are comprised of wire of adiameter of less than 0.04 inches. According to some embodiments, thehalf loops 360 are comprised of wire of a diameter of less than 0.03inches. According to some embodiments, the half loops 360 are comprisedof wire of a diameter of less than 0.02 inches. According to someembodiments, the half loops 360 are comprised of wire of a diameter ofless than 0.01 inches. According to some embodiments, the half loops 360are comprised of wire of a diameter of less than 0.009 inches. Accordingto some embodiments, the half loops 360 are comprised of wire of adiameter of less than 0.008 inches. According to some embodiments, thehalf loops 360 are comprised of wire of a diameter of less than 0.007inches. According to some embodiments, the half loops 360 are comprisedof wire of a diameter of less than 0.006 inches. According to someembodiments, the half loops 360 are comprised of wire of a diameter ofless than 0.005 inches. According to some embodiments, the half loops360 are comprised of wire of a diameter of less than 0.004 inches.According to some embodiments, the half loops 360 are comprised of wireof a diameter of less than 0.003 inches. According to some embodiments,the half loops 360 are comprised of wire of a diameter of less than0.002 inches. According to some embodiments, the half loops 360 arecomprised of wire of a diameter of less than 0.001 inches.

According to some embodiments, a plurality of half loops 360 isconnected around the circumference of the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 10 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 20 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 30 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 40 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 50 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 60 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 70 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 80 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 90 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 100 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 120 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 130 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 140 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 150 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 160 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 170 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 180 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 190 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 200 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 210 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 220 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 230 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 240 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 250 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 260 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 270 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 280 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 290 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 300 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 310 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 320 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 330 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 340 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 350 degrees of rotation around the central tube 390. According tosome embodiments, the half loops 360 are located on the central tube 390every 360 degrees of rotation around the central tube 390.

According to some embodiments, the half loops 360 are staggered so thateach half loop at least partially overlaps with at least one other halfloop 360. For example, as depicted in FIG. 5A the half loops arepositioned around the circumference of the central tube 390 every 180degrees and are staggered so that each half loop 360 overlaps with thepreceding and following half loop 360. In the embodiment depicted inFIG. 5A, about 33% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 10% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 15% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 20% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 25% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 30% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 35% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 40% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 45% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 50% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 60% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 65% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 70% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 75% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 80% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 85% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 90% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 95% of a preceding half loop 360 overlaps with afollowing half loop 360. According to some embodiments, the half loops360 are staggered around the circumference of the central tube 390 sothat less than 100% of a preceding half loop 360 overlaps with afollowing half loop 360.

According to some embodiments, the half loops 360 may be staggeredaround the circumference of the central tube 390 so that a precedinghalf loop does not overlap with a following half loop 360.

According to some embodiments, the half loop 360 comprises cross strutwires 380 that are connected to the central tube 390 at a 90-degreeangle relative to the central tube 390. According to some embodiments,the cross-strut wires 380 are connected to the central tube 390 at lessthan a 90-degree angle. According to some embodiments, the cross-strutwires 380 are connected to the central tube 390 at less than an85-degree angle. According to some embodiments, the cross-strut wires380 are connected to the central tube 390 at less than an 80-degreeangle. According to some embodiments, the cross-strut wires 380 areconnected to the central tube 390 at less than a 75-degree angle.According to some embodiments, the cross-strut wires 380 are connectedto the central tube 390 at less than a 70-degree angle. According tosome embodiments, the cross-strut wires 380 are connected to the centraltube 390 at less than a 65-degree angle. According to some embodiments,the cross-strut wires 380 are connected to the central tube 390 at lessthan a 60-degree angle. According to some embodiments, the cross-strutwires 380 are connected to the central tube 390 at less than a 55-degreeangle. According to some embodiments, the cross-strut wires 380 areconnected to the central tube 390 at less than a 50-degree angle.According to some embodiments, the cross-strut wires 380 are connectedto the central tube 390 at less than a 45-degree angle. According tosome embodiments, the cross-strut wires 380 are connected to the centraltube 390 at less than a 40-degree angle. According to some embodiments,the cross-strut wires 380 are connected to the central tube 390 at lessthan a 35-degree angle. According to some embodiments, the cross-strutwires 380 are connected to the central tube 390 at less than a 30-degreeangle. According to some embodiments, the cross-strut wires 380 areconnected to the central tube 390 at less than a 25-degree angle.According to some embodiments, the cross-strut wires 380 are connectedto the central tube 390 at less than a 20-degree angle. According tosome embodiments, the cross-strut wires 380 are connected to the centraltube 390 at less than a 15-degree angle. According to some embodiments,the cross-strut wires 380 are connected to the central tube 390 at lessthan a 10-degree angle. According to some embodiments, the cross-strutwires 380 are connected to the central tube 390 at less than a 5-degreeangle.

According to some embodiments, the half loop structures 360 comprisebetween 1 and 100 cross strut wires 380. According to some embodiments,the half loop structures 360 comprise 1 or more cross strut wires 380.According to some embodiments, the half loop structures 360 comprise 2or more cross strut wires 380. According to some embodiments, the halfloop structures 360 comprise 3 or more cross strut wires 380. Accordingto some embodiments, the half loop structures 360 comprise 4 or morecross strut wires 380. According to some embodiments, the half loopstructures 360 comprise 5 or more cross strut wires 380. According tosome embodiments, the half loop structures 360 comprise 6 or more crossstrut wires 380. According to some embodiments, the half loop structures360 comprise 7 or more cross strut wires 380. According to someembodiments, the half loop structures 360 comprise 8 or more cross strutwires 380. According to some embodiments, the half loop structures 360comprise 9 or more cross strut wires 380. According to some embodiments,the half loop structures 360 comprise 10 or more cross strut wires 380.According to some embodiments, the half loop structures 360 comprise 15or more cross strut wires 380. According to some embodiments, the halfloop structures 360 comprise 20 or more cross strut wires 380. Accordingto some embodiments, the half loop structures 360 comprise 25 or morecross strut wires 380. According to some embodiments, the half loopstructures 360 comprise 30 or more cross strut wires 380. According tosome embodiments, the half loop structures 360 comprise 40 or more crossstrut wires 380. According to some embodiments, the half loop structures360 comprise 50 or more cross strut wires 380. According to someembodiments, the half loop structures 360 comprise 60 or more crossstrut wires 380. According to some embodiments, the half loop structures360 comprise 70 or more cross strut wires 380. According to someembodiments, the half loop structures 360 comprise 80 or more crossstrut wires 380. According to some embodiments, the half loop structures360 comprise 90 or more cross strut wires 380. According to someembodiments, the half loop structures 360 comprise 100 or more crossstrut wires 380.

According to some embodiments, the half loop structures 360 on themacerating irrigation catheter 300 are positioned on the central tube390 above or adjacent to one or more of the side holes 330. According tosome embodiments, the half loop structures 360 positioned on the centraltube 390 above or adjacent to a side hole 330 are effective to break upthe clot into smaller pieces, thereby facilitating its removal via anaspirating catheter proximal or distal to the clot, while alsominimizing the chance the aspirating catheter could become clogged bylarger pieces of clot. According to some embodiments, the type andamount of breakdown of clots into smaller pieces can be altereddepending upon the number and position of the microwire 370 and crossstrut wires 380 in proximity to the side holes 330.

According to some embodiments, the microwire 370 spans at least a partof a side hole 330, and all concomitant cross strut wires 380 are on oneside of the side hole 330. According to the embodiment illustrated inFIG. 5B, the microwire 370 spans the middle of the side hole 330, andeach of cross strut wires 380 are connected to the surface of thecentral tube 390 on one side of the side hole 330.

According to some embodiments, the microwire 370 spans at least part ofa side hole 330 and the concomitant cross strut wires are connected toeither side of the side hole 330. According to the embodimentillustrated in FIG. 5C, the microwire 370 spans the middle of the sidehole 330, and each of cross strut wires 380 are alternately connected tothe central tube 390 on opposite sides of the side hole 330, or atvarious angles relative to the side holes.

According to some embodiments, the microwire 370 is connected to thecentral tube 390 such that the microwire 370 is adjacent to, but doesnot span, side holes 330. According to the embodiment illustrated inFIG. 5D, the microwire 370 is connected to the central tube 390 betweentwo separate side holes 330. Cross strut wires 380 are also connected tothe central tube 390 between two separate side holes 330.

According to some embodiments of the described invention, the length ofthe microwire 370 and the length of the cross-strut wires 380 determinethe distance by which the half loop structures extend from the surfaceof the central tube 390. According to some embodiments, one or more ofthe half loop structures 360 extend from the surface of the central tube390 by a length equivalent to one half the diameter of the central tube390. According to some embodiments, one or more of the half loopstructures 360 extend from the surface of the central tube 390 by alength equivalent to the diameter of the central tube 390. According tosome embodiments, one or more of the half loop structures 360 extendfrom the surface of the central tube 390 by a length equivalent todouble the diameter of the central tube 390. According to someembodiments, one or more of the half loop structures 360 extend from thesurface of the central tube 390 by a length equivalent to triple thediameter of the central tube 390. According to some embodiments, one ormore of the half loop structures 360 extend from the surface of thecentral tube 390 by a length equivalent to quadruple the diameter of thecentral tube 390. According to some embodiments, one or more of the halfloop structures 360 extend from the surface of the central tube 390 by alength equivalent to five times the diameter of the central tube 390.According to some embodiments, one or more of the half loop structures360 extend from the surface of the central tube 390 by a lengthequivalent to six times the diameter of the central tube 390. Accordingto some embodiments, one or more of the half loop structures 360 extendfrom the surface of the central tube 390 by a length equivalent to lessthan one half the diameter of the central tube 390. According to someembodiments, one or more of the half loop structures 360 extend from thesurface of the central tube 390 by a length equivalent to greater thansix times the diameter of the central tube 390.

According to some embodiments, the microwire 370 takes a continuouslycurved path between the first end and the second end. According to someembodiments, the microwire 370 takes an irregularly shaped path betweenthe first end and the second end. According to some embodiments, themicrowire 370 takes a path comprising two or more straight pathsconnected at an angle between 0 degrees and 180 degrees.

According to some embodiments, the cross-strut wires 380 take a straightpath from a first end connected to the central tube 390 and the secondend connected to the microwire 370. According to some embodiments, thecross-strut wires 380 take a non-linear path from a first end connectedto the central tube 390 and the second end connected to the microwire370. According to some embodiments, cross strut wires 380 are branchedsuch that one or more of the cross-strut wires 380 is connected to oneor more other cross strut wires 380.

According to some embodiments, the half loop structures 360 are orientedlinearly along the central tube 390; i.e. the first end of the microwire370 and the second end of the microwire 370 are attached to the centraltube 390 in a line parallel to the length of the central tube 390.According to some embodiments, the half loop structures 360 are orientedin a spiral around the central tube 390; i.e., the second end of themicrowire 370 is located in a position on the surface of the centraltube 390 that is radially twisted around the central tube 390 relativeto the first end of the microwire 370. According to some embodiments,the second end of the microwire 370 is radially twisted relative to thefirst end of the microwire 370 by less than 5 degrees. According to someembodiments, the second end of the microwire 370 is radially twistedrelative to the first end of the microwire 370 by less than 10 degrees.According to some embodiments, the second end of the microwire 370 isradially twisted relative to the first end of the microwire 370 by lessthan 15 degrees. According to some embodiments, the second end of themicrowire 370 is radially twisted relative to the first end of themicrowire 370 by less than 20 degrees. According to some embodiments,the second end of the microwire 370 is radially twisted relative to thefirst end of the microwire 370 by less than 25 degrees. According tosome embodiments, the second end of the microwire 370 is radiallytwisted relative to the first end of the microwire 370 by less than 30degrees. According to some embodiments, the second end of the microwire370 is radially twisted relative to the first end of the microwire 370by less than 35 degrees. According to some embodiments, the second endof the microwire 370 is radially twisted relative to the first end ofthe microwire 370 by less than 40 degrees. According to someembodiments, the second end of the microwire 370 is radially twistedrelative to the first end of the microwire 370 by less than 45 degrees.According to some embodiments, the second end of the microwire 370 isradially twisted relative to the first end of the microwire 370 by lessthan 50 degrees. According to some embodiments, the second end of themicrowire 370 is radially twisted relative to the first end of themicrowire 370 by less than 60 degrees. According to some embodiments,the second end of the microwire 370 is radially twisted relative to thefirst end of the microwire 370 by less than 65 degrees. According tosome embodiments, the second end of the microwire 370 is radiallytwisted relative to the first end of the microwire 370 by less than 70degrees. According to some embodiments, the second end of the microwire370 is radially twisted relative to the first end of the microwire 370by less than 75 degrees. According to some embodiments, the second endof the microwire 370 is radially twisted relative to the first end ofthe microwire 370 by less than 80 degrees. According to someembodiments, the second end of the microwire 370 is radially twistedrelative to the first end of the microwire 370 by less than 85 degrees.According to some embodiments, the second end of the microwire 370 isradially twisted relative to the first end of the microwire 370 by lessthan 90 degrees. According to some embodiments, the second end of themicrowire 370 is radially twisted relative to the first end of themicrowire 370 by less than 180 degrees. According to some embodiments,the second end of the microwire 370 is radially twisted relative to thefirst end of the microwire 370 by less than 360 degrees. According tosome embodiments, the second end of the microwire 370 is radiallytwisted relative to the first end of the microwire 370 by less than 720degrees. According to some embodiments, the second end of the microwire370 is radially twisted relative to the first end of the microwire 370by less than 1080 degrees.

According to some embodiments, the macerating irrigation microcatheter300 is adapted so that fluid passes through the catheter as it ismacerating the clot, for example, in short intermittent infusions; forexample, in a continuous infusion. According to some embodiments, thefluid flow is into and beyond the clot so that the clot is capable ofbeing aspirated proximally.

According to some embodiments, the macerating irrigation catheter 300further comprises a filter 395 that protrudes from the distal end of thecentral tube 390 to catch any macerated clot material that escapesaspiration. According to some embodiments, the filter 395 is connectedto an intraluminal cable 396 which runs through the luminal spacedefined by the central tube 390 (FIG. 5A). According to someembodiments, the filter 395 comprises a net structure connected to theintraluminal cable 396, wherein the net structure is effective tocapture distal emboli that may result from maceration of a blood clotproximal to the filter. According to some embodiments, the filter 395 iseffective to capture particulates greater than 10 μm in size. Accordingto some embodiments, the filter 395 is effective to capture particulatesgreater than 15 μm in size. According to some embodiments, the filter395 is effective to capture particulates greater than 20 μm in size.According to some embodiments, the filter 395 is effective to captureparticulates greater than 30 μm in size. According to some embodiments,the filter 395 is effective to capture particulates greater than 40 μmin size. According to some embodiments, the filter 395 is effective tocapture particulates greater than 50 μm in size. According to someembodiments, the filter 395 is effective to capture particulates greaterthan 70 μm in size. According to some embodiments, the filter 395 iseffective to capture particulates greater than 100 μm in size. Accordingto some embodiments, the filter 395 is effective to capture particulatesgreater than 500 μm in size.

According to some embodiments, the filter 395 comprises an opening thatis round in shape and comprises a diameter approximately equal to thediameter of the central tube 390. According to some embodiments, thefilter 395 comprises an opening that comprises a diameter less than orequal to twice the diameter of the central tube 390. According to someembodiments, the filter 395 comprises an opening that comprises adiameter less than or equal to three times the diameter of the centraltube 390. According to some embodiments, the filter 395 comprises anopening that comprises a diameter less than or equal to four times thediameter of the central tube 390. According to some embodiments, thefilter 395 comprises an opening that comprises a diameter less than orequal to five times the diameter of the central tube 390. According tosome embodiments, the filter 395 comprises an opening that comprises adiameter less than or equal to six times the diameter of the centraltube 390. According to some embodiments, the filter 395 comprises anopening that comprises a diameter less than or equal to seven times thediameter of the central tube 390. According to some embodiments, thefilter 395 comprises an opening that comprises a diameter less than orequal to eight times the diameter of the central tube 390. According tosome embodiments, the filter 395 comprises an opening that comprises adiameter less than or equal to nine times the diameter of the centraltube 390. According to some embodiments, the filter 395 comprises anopening that comprises a diameter less than or equal to ten times thediameter of the central tube 390.

According to some embodiments, diameter of the filter 395 diameter isbetween 0.1 cm and 15 cm. According to some embodiments, diameter of thefilter 395 diameter is less than or equal to 15 cm. According to someembodiments, diameter of the filter 395 diameter is less than or equalto 10 cm. According to some embodiments, diameter of the filter 395 isless than or equal to 7 cm. According to some embodiments, diameter ofthe filter 395 is less than or equal to 5 cm. According to someembodiments, diameter of the filter 395 is less than or equal to 3 cm.According to some embodiments, diameter of the filter 395 is less thanor equal to 1 cm. According to some embodiments, diameter of the filter395 is less than or equal to 0.5 cm.

According to some embodiments the filter 395 is made from a flexible,but resilient material that can be folded and contained inside the lumendefined by central tube 390.

FIG. 6 shows an embodiment of the aspiration catheter that is largeenough that it is sufficiently occlusive to occlude the vessel so thatthere is no anterograde flow distally into the brain. According to somesuch embodiments, aspiration is in the direction of flow. According tosome such embodiments, aspiration is opposite the direction of flow. Insome embodiments, as depicted in FIG. 6, there is a balloon 430 mountedon the outside of the distal segment of the aspiration catheter, whichcan help occlude the vessel in some cases. In some illustrative cases,flow of clot into the aspiration catheter can then be augmented by acombination of maceration by the rotating wire loops 360 which breaksthe clot into smaller pieces that can be more readily sucked up withoutoccluding the aspiration catheter, as well irrigation into and beyondthe clot, which serves to expand that segment of the vessel, therebydecreasing adherence of the clot to the vessel wall, and also serves toreplace the clot and any blood that is sucked out of the vessel, therebyavoiding an “empty vacuum” phenomenon, which can cause the vessel tocollapse and nothing to flow when aspiration is applied. In otherembodiments an aspiration catheter without a balloon can be used, butthe aspiration catheter is chosen to be of the same size or slightlylarger than the target vessel, so when it is advanced into the targetvessel it becomes wedged against the vessel walls, thereby obstructingnormal distal flow.

As illustrated in FIG. 6, according to some embodiments, theendovascular device of the described invention may comprise an aspirator400 comprising a proximal end 410 and a distal end 420, wherein thewalls of the aspirator 400 define a lumen. As seen in FIG. 6, themacerating irrigation microcatheter 300 may protrude from the lumen ofthe aspirator 400 on the distal end of the aspirator 400.

According to some embodiments, the diameter of the central tube 390 ofthe macerating irrigation microcatheter 300 can be less than thediameter of the aspirator 400. According to some embodiments, the ratioof the diameter of the central tube 390 to the diameter of the aspirator400 is less than 1:100. According to some embodiments, the ratio of thediameter of the central tube 390 to the diameter of the aspirator 400 isless than 1:50. According to some embodiments, the ratio of the diameterof the central tube 390 to the diameter of the aspirator 400 is lessthan 1:25. According to some embodiments, the ratio of the diameter ofthe central tube 390 to the diameter of the aspirator 400 is less than1:20. According to some embodiments, the ratio of the diameter of thecentral tube 390 to the diameter of the aspirator 400 is less than 1:15.According to some embodiments, the ratio of the diameter of the centraltube 390 to the diameter of the aspirator 400 is less than 1:10.According to some embodiments, the ratio of the diameter of the centraltube 390 to the diameter of the aspirator 400 is less than 1:5.According to some embodiments, the ratio of the diameter of the centraltube 390 to the diameter of the aspirator 400 is less than 1:4.According to some embodiments, the ratio of the diameter of the centraltube 390 to the diameter of the aspirator 400 is less than 1:3.According to some embodiments, the ratio of the diameter of the centraltube 390 to the diameter of the aspirator 400 is less than 1:2.

According to some embodiments, the aspirator 400 is connected to aninflatable soft balloon 430 that is effective to expand to the size of ablood vessel to occlude the blood vessel so that there is no anterogradeflow distally into the brain. According to some embodiments, the softballoon 430 is located on the distal end 420 of the aspirator 400.

FIGS. 7A and 7B show exemplary and non-limiting embodiments of theendovascular device of the described invention. As seen in FIG. 7A amicrocatheter 100, as described above, is connected to, and in someversions the proximal portion is embedded within, the inner walldefining the lumen of an aspirator 400. According to some embodiments,the connection of the microcatheter 100 to the inner wall defining thelumen of the aspirator 400 maximizes the force of aspiration that can beapplied to a clot by the aspirator 400. According to some embodiments,the flow of fluid in the distal to proximal direction in the aspiratoris laminar. According to some embodiments, the flow of fluid in theproximal to distal direction in the microcatheter is laminar. Accordingto some embodiments, the flow rate of fluid in the aspirator ormicrocatheter is described by Poiseuille's Law:

Volume Flowrate=(Pressure difference×radius4)/(8/π×viscosity×length)

As seen in FIG. 7B a microcatheter 100, as described above, is connectedto the inner wall defining the lumen of an aspirator 400, wherein theaspirator is additionally connected to a soft balloon 430.

FIG. 7C shows a non-limiting example of one aspect of the endovasculardevice of the present invention. According to some embodiments, themicrocatheter is positioned between an inner wall 900 and outer wall 910of the aspirator, wherein the inner wall defines a first luminal space920 and the outer wall defines a second luminal space 930, and whereinthe inner wall and first luminal space are disposed within the secondluminal space. According to some embodiments, the microcatheter 100 isdisposed in the second luminal space between the inner wall and theouter wall. According to some embodiments, the distal end of the secondluminal space is sealed with the microcatheter projected through in aproximal to distal direction. According to some embodiments, themicrocatheter runs the full length of the second luminal space.According to some embodiments, the microcatheter runs less than the fulllength of the second luminal space. According to some embodiments, thesecond luminal space is continuous with the luminal space defined by themicrocatheter. According to some embodiments, a fluid is introduced intothe second luminal space on the proximal end and ejected out from themicrocatheter on the distal end, while simultaneously the first luminalspace aspirates fluid in a distal to proximal direction. According tosome embodiments, fluid flows through the second luminal space in adistal to proximal direction and funnels to one side into the lumen ofthe microcatheter. According to some embodiments, the microcatheter isdisposed in the second lumen between the inner wall and outer wall, andis adapted to receive fluid which flows from the proximal end of themicrocatheter to the distal end of the microcatheter.

According to some embodiments, the inflatable space defined by the softballoon is connected to the first luminal space, which allows fluid tobe injected into the soft balloon via the first luminal space fromoutside the patient's blood vessel. The second luminal space is aseparate compartment from the first luminal space and is capable ofsuctioning fluid and particulates from the patient's blood vesseloutside the patient's body.

According to some embodiments, the second luminal space is furtherdivided into two or more separate spaces by a divider 940 that isconnected to the inner wall and the outer wall, and that runs along thelength of the inner wall and outer wall (FIG. 7D). According to someembodiments, the second luminal space is divided into a firstcompartment 950 and a second compartment 960. According to someembodiments, the first compartment is continuous with the lumen of themicrocatheter, and the second compartment is continuous with an innerspace defined by the soft balloon 430. According to some embodiments,the first compartment is adapted to flow fluid from the proximal end tothe distal end of the aspirator and out the distal end of themicrocatheter, and the second compartment is adapted to flow fluid intoand out of the inner space defined by the soft balloon.

According to some embodiments, the described invention comprises a tubedefined by an outer wall 950 and two or more inner walls 960, whereinthe inner walls run as least part of the length of the outer wall anddefine two or more luminal spaces 970 (FIG. 7E). According to someembodiments, one or more of the luminal spaces 970 is continuous withone or more lumens of microcatheters. According to some embodiments, oneor more of the luminal spaces 970 is continuous with one or more innerspaces defined by one or more soft balloons. According to someembodiments, one or more of the luminal spaces is adapted to flow fluidfrom the proximal end to the distal end of the aspirator and out thedistal end of the microcatheter, and one or more of the luminal spacesis adapted to flow fluid into and out of the inner space define by thesoft balloon.

According to some embodiments, the described invention comprises aY-connector that includes two Luer Locks which connect two or more ofthe lumens defined as shown in any of FIG. 7C, 7D, 7E, or 7J such thatfunctionally there is a separate lumen for aspiration and a separatelumen for irrigation. According to some embodiments, the presentinvention comprises a connector including Luer Locks which connect twoor more of the lumens defined as shown in any of FIG. 7C, 7D, 7E, or 7Jsuch that the separate lumens merge into one lumen outside the patient'sbody, wherein the path of fluid flow can be selected. According to someembodiments, one or more distinct lumens is/are bounded by a singlestructure on the distal end (e.g., FIG. 7C, 7D, 7E, or 7J), while eachlumen diverges into separate branches defined by separate structures onthe proximal end. According to some embodiments, the distal one or moredistinct lumens bounded by a single structure is/are adapted to beinserted into a blood vessel, while the proximal divergent lumensdefined by separate structures remain outside a blood vessel. Accordingto some embodiments, the proximal divergent lumens defined by separatestructures are connected to a separate Luer Lock for each lumen.

According to some embodiments, one or more of the lumens shown in any ofembodiments FIG. 7C, 7D, 7E, or 7J is adapted for one or more of ballooninflation, contrast, aspiration, and irrigation. According to someembodiments, a Luer Lock is attached to the proximal end of each lumen.

According to some embodiments, the diameter of the soft balloon 430ranges from about 1 mm to about 100 mm. According to some embodiments,the diameter of the soft balloon 430 is about 1 mm. According to someembodiments, the diameter of the soft balloon 430 is about 2 mm.According to some embodiments, the diameter of the soft balloon 430 isabout 3 mm. According to some embodiments, the diameter of the softballoon 430 is about 4 mm. According to some embodiments, the diameterof the soft balloon 430 is about 5 mm. According to some embodiments,the diameter of the soft balloon 430 is about 10 mm. According to someembodiments, the diameter of the soft balloon 430 is about 15 mm.According to some embodiments, the diameter of the soft balloon 430 isabout 20 mm. According to some embodiments, the diameter of the softballoon 430 is about 25 mm. According to some embodiments, the diameterof the soft balloon 430 is about 30 mm. According to some embodiments,the diameter of the soft balloon 430 is about 35 mm. According to someembodiments, the diameter of the soft balloon 430 is about 40 mm.According to some embodiments, the diameter of the soft balloon 430 isabout 45 mm. According to some embodiments, the diameter of the softballoon 430 is about 50 mm.

According to some embodiments, the length of the soft balloon 430 rangesfrom about 1 mm to about 1000 mm. According to some embodiments, thelength of the soft balloon 430 is about 4 mm. According to someembodiments, the length of the soft balloon 430 is about 5 mm. Accordingto some embodiments, the length of the soft balloon 430 is about 6 mm.According to some embodiments, the length of the soft balloon 430 isabout 7 mm. According to some embodiments, the length of the softballoon 430 is about 8 mm. According to some embodiments, the length ofthe soft balloon 430 is about 9 mm. According to some embodiments, thelength of the soft balloon 430 is about 10 mm. According to someembodiments, the length of the soft balloon 430 is about 20 mm.According to some embodiments, the length of the soft balloon 430 isabout 30 mm. According to some embodiments, the length of the softballoon 430 is about 40 mm. According to some embodiments, the length ofthe soft balloon 430 is about 50 mm. According to some embodiments, thelength of the soft balloon 430 is about 60 mm. According to someembodiments, the length of the soft balloon 430 is about 70 mm.According to some embodiments, the length of the soft balloon 430 isabout 80 mm. According to some embodiments, the length of the softballoon 430 is about 90 mm. According to some embodiments, the length ofthe soft balloon 430 is about 100 mm. According to some embodiments, thelength of the soft balloon 430 is about 110 mm. According to someembodiments, the length of the soft balloon 430 is about 120 mm.According to some embodiments, the length of the soft balloon 430 isabout 130 mm. According to some embodiments, the length of the softballoon 430 is about 140 mm. According to some embodiments, the lengthof the soft balloon 430 is about 150 mm. According to some embodiments,the length of the soft balloon 430 is about 160 mm. According to someembodiments, the length of the soft balloon 430 is about 170 mm.According to some embodiments, the length of the soft balloon 430 isabout 180 mm. According to some embodiments, the length of the softballoon 430 is about 190 mm. According to some embodiments, the lengthof the soft balloon 430 is about 200 mm. According to some embodiments,the length of the soft balloon 430 is about 210 mm. According to someembodiments, the length of the soft balloon 430 is about 220 mm.According to some embodiments, the length of the soft balloon 430 isabout 230 mm. According to some embodiments, the length of the softballoon 430 is about 240 mm. According to some embodiments, the lengthof the soft balloon 430 is about 250 mm. According to some embodiments,the length of the soft balloon 430 is about 260 mm. According to someembodiments, the length of the soft balloon 430 is about 270 mm.According to some embodiments, the length of the soft balloon 430 isabout 280 mm. According to some embodiments, the length of the softballoon 430 is about 290 mm. According to some embodiments, the lengthof the soft balloon 430 is about 300 mm. According to some embodiments,the length of the soft balloon 430 is about 350 mm. According to someembodiments, the length of the soft balloon 430 is about 400 mm.According to some embodiments, the length of the soft balloon 430 isabout 450 mm. According to some embodiments, the length of the softballoon 430 is about 500 mm. According to some embodiments, the lengthof the soft balloon 430 is about 550 mm. According to some embodiments,the length of the soft balloon 430 is about 600 mm. According to someembodiments, the length of the soft balloon 430 is about 650 mm.According to some embodiments, the length of the soft balloon 430 isabout 700 mm. According to some embodiments, the length of the softballoon 430 is about 750 mm. According to some embodiments, the lengthof the soft balloon 430 is about 800 mm. According to some embodiments,the length of the soft balloon 430 is about 850 mm. According to someembodiments, the length of the soft balloon 430 is about 900 mm.According to some embodiments, the length of the soft balloon 430 isabout 1000 mm.

According to some embodiments, the soft balloon 430 comprises variousshapes including, but not limited, cylindrical, spherical, oval,conical, stepped, tapered and dog bone.

According to some embodiments, the soft balloon 430 comprises a materialsuch as, for example, a polyamide, polyethylene terephthalate (PET),polyurethane, composites, and engineered nylons. Engineered nylonsinclude, but are not limited to, Pebax®, Grilamid®, and Vestamid® orother suitable materials.

According to some embodiments, the soft balloon 430 ends comprisevarious shapes including, but not limited to, a conical sharp corner, aconical radius corner, an offset neck, a spherical end and a square.

According to some embodiments, the soft balloon 430 is filled with afluid. Non-limiting examples of the fluid include sterile water,contrast, and saline.

According to some embodiments, the soft balloon 430 is adapted toocclude proximally blood flow and, in conjunction with irrigation andaspiration, to reverse the direction of flow in the blood vessel and/orto prevent the distal flow of emboli.

According to some embodiments, the aspirator is adapted to captureemboli during procedures where the direction of blood flow relative tothe aspirator is from the distal end to the proximal end. According tosome embodiments, the aspirator 800 comprises a flared distal end 820that is capable of capturing emboli as blood flows in a distal end toproximal end direction (FIGS. 7F to 7I). According to some embodiments,the flared distal end 820 is adapted to guide emboli into the flaredaspirator 800 for removal from the blood vessel.

According to some embodiments, the diameter of the opening at the flareddistal end 820 of the flared aspirator 800 is at least 10% greater thanthe diameter of the proximal end 810. According to some embodiments, thediameter of the opening of the flared distal end 820 of the flaredaspirator 800 is at least 15% greater than the diameter of the proximalend 810. According to some embodiments, the diameter of the opening ofthe flared distal end 820 of the flared aspirator 800 is at least 20%greater than the diameter of the proximal end 810. According to someembodiments, the diameter of the opening of the flared distal end 820 ofthe flared aspirator 800 is at least 25% greater than the diameter ofthe proximal end 810. According to some embodiments, the diameter of theopening of the flared distal end 820 of the flared aspirator 800 is atleast 30% greater than the diameter of the proximal end 810. Accordingto some embodiments, the diameter of the opening of the flared distalend 820 of the flared aspirator 800 is at least 35% greater than thediameter of the proximal end 810. According to some embodiments, thediameter of the opening of the flared distal end 820 of the flaredaspirator 800 is at least 40% greater than the diameter of the proximalend 810. According to some embodiments, the diameter of the opening ofthe flared distal end 820 of the flared aspirator 800 is at least 50%greater than the diameter of the proximal end 810. According to someembodiments, the diameter of the opening of the flared distal end 820 ofthe flared aspirator 800 is at least 60% greater than the diameter ofthe proximal end 810. According to some embodiments, the diameter of theopening of the flared distal end 820 of the flared aspirator 800 is atleast 65% greater than the diameter of the proximal end 810. Accordingto some embodiments, the diameter of the opening of the flared distalend 820 of the flared aspirator 800 is at least 70% greater than thediameter of the proximal end 810. According to some embodiments, thediameter of the opening of the flared distal end 820 of the flaredaspirator 800 is at least 75% greater than the diameter of the proximalend 810. According to some embodiments, the diameter of the opening ofthe flared distal end 820 of the flared aspirator 800 is at least 80%greater than the diameter of the proximal end 810. According to someembodiments, the diameter of the opening of the flared distal end 820 ofthe flared aspirator 800 is at least 85% greater than the diameter ofthe proximal end 810. According to some embodiments, the diameter of theopening of the flared distal end 820 of the flared aspirator 800 is atleast 90% greater than the diameter of the proximal end 810. Accordingto some embodiments, the diameter of the opening of the flared distalend 820 of the flared aspirator 800 is at least 95% greater than thediameter of the proximal end 810. According to some embodiments, thediameter of the opening of the flared distal end 820 of the flaredaspirator 800 is at least 100% greater than the diameter of the proximalend 810. According to some embodiments, the diameter of the opening ofthe flared distal end 820 of the flared aspirator 800 is at least 200%greater than the diameter of the proximal end 810. According to someembodiments, the diameter of the opening of the flared distal end 820 ofthe flared aspirator 800 is at least 300% greater than the diameter ofthe proximal end 810. According to some embodiments, the diameter of theopening of the flared distal end 820 of the flared aspirator 800 is atleast 400% greater than the diameter of the proximal end 810. Accordingto some embodiments, the diameter of the opening of the flared distalend 820 of the flared aspirator 800 is at least 500% greater than thediameter of the proximal end 810. According to some embodiments, thediameter of the opening of the flared distal end 820 of the flaredaspirator 800 is at least 600% greater than the diameter of the proximalend 810. According to some embodiments, the diameter of the opening ofthe flared distal end 820 of the flared aspirator 800 is at least 700%greater than the diameter of the proximal end 810. According to someembodiments, the diameter of the opening of the flared distal end 820 ofthe flared aspirator 800 is at least 800% greater than the diameter ofthe proximal end 810. According to some embodiments, the diameter of theopening of the flared distal end 820 of the flared aspirator 800 is atleast 900% greater than the diameter of the proximal end 810. Accordingto some embodiments, the diameter of the opening of the flared distalend 820 of the flared aspirator 800 is at least 1000% greater than thediameter of the proximal end 810.

According to some embodiments, the flared distal end 820 is a continuousextension of the flared or unflared aspirator 800. According to someembodiments, the flared aspirator comprises a solid structure thatobstructs blood flow (FIG. 7F). According to some embodiments, theflared distal end comprises a mesh material that is adapted to captureemboli, but also allow passage of blood flow (FIG. 7G). By allowingcontinued blood flow through the mesh filter attached to the distal endof the aspiration catheter, the aspiration can be applied onlyintermittently, to clear thrombi and other debris from the filter. Theamount of flow versus flow obstruction can be monitored by intermittentcontrast venography, or by transabdominal ultrasound. Alternatively, insome iterations IVUS (intravascular or intravenus ultrasound) can beincorporated into the tip of the aspiration catheter, to allowcontinuous monitoring of blood flow at the tip of the aspirationcatheter without the use of contrast, radiation, or a second technicianperforming transabdominal ultrasound. By way of nonlimiting example, thefollowing setup can be used in a patient with a large left Iliac Veinthrombus: Venous access can be obtained via the left Femoral Vein, andseparately through either Internal Jugular Vein in the neck. At thejugular vein an aspiration catheter with embedded IVUS andpo a flaredfilter end extension can be advanced and deployed in the upper InferiorVena Cava, with the end hole for aspiration and the filter facinginferiorly, so as to be oriented to capture any debris as it flows inthe normal venous direction from the leg to the heart. A rotationalirrigating thrombectomy hypotube with side wire loops can then beadvanced from the left femoral vein access across the clot in the leftiliac vein. The IVUS can then start monitoring flow in the upper IVC atthe tip of the aspiration catheter. But in order to minimize blood loss,aspiration is not started until some diminution of flow and buildup ofembolic debris is seen. The rotational maceration and aspiration arethen started, to break up and free up the clot form the iliac vein. Asflow is restored in the iliac vein, debris flows to the IVC and iscaptured in the filter. Intermittent aspiration can then be applied asneeded only, to minimize blood loss. In some cases, another rotationalseparator, with or without an additional irrigating element, can beadvanced though the aspiration catheter, to further break up the clotand debris into smaller pieces when needed, to avoid the aspirationcatheter becoming clogged. In other iterations the aspiration cathetercan additionally have a wire through it hat ends inside the catheter inthe tip, and uses technology to create vibrational energy, similar tothe used in the Penumbra Apollo device to remove parenchymal blood fromthe brain, to break up the clots as they enter the tipoff the aspirationcatheter, and thereby avoid clogging of the aspiration catheter.

The present invention in one embodiment includes a vibrational wire isdeployed distally from or within said device. Said vibrational wire isdesigned to cut clots.

According to some embodiments, the flaring of the flared end 820 is acontinuously increasing flare relative to the rest of the aspirator 800,which gives the outer wall of the flared end 820 a concave shape (FIG.7F). According to some embodiments, the flaring of the flared end 820 isabrupt and provides the outer wall of the flared end 820 with a flatshape (FIG. 7H) or a convex shape (FIG. 7I).

According to some embodiments, the diameter of the opening of the flareddistal end 820 is capable of being increased or decreased relative tothe diameter of the rest of the flared aspirator 800 while placed insidea blood vessel. According to some embodiments, the diameter of theopening of the flared distal end 820 is increased by inflation of aballoon attached to the inner or outer wall of the flared distal end 820or embedded within the wall of the flared distal end 820. According tosome embodiments, the flared distal end 820 is adapted to be retractedinside the lumen of the flared aspirator 800. According to someembodiments, the flared distal end 820 is made of a flexible, resilientmaterial with a flared shape that expands while protruding from theflared aspirator 800 and collapses when retracted into the flaredaspirator 800. According to some embodiments, the flared distal end 820is adapted to cinch closed via a lasso mechanism around the periphery ofthe flared distal end 820. According to some embodiments, the flaredaspirator 800 further comprises a macerating irrigation catheter 300 asshown and described.

Referring now to FIG. 7K, according to embodiments having flared distalend 820 adapted to cinch closed via a lasso mechanism, said lassomechanism is comprised of at least one string or wire 821 extending froman external reel or retraction mechanism 822. String 821 passes throughflared aspirator 800 through a lasso channel 823. String 821 is fixed toperiphery of flared distal end 820 at single point 824. From fixed point824, said string travels circumferentially around said periphery offlared distal end 820 slidably through hoops 825 forming a loop or lassoabout the rim. In an alternative embodiment, hoops 825 are replaced by asecond lasso channel (not shown).

In operation, using the lasso mechanism of FIG. 7K, flared distal end820 of flared aspirator 800 is cinched closed by retracting string 821by rewinding reel 822 (or other mechanism adapted to ratchet backstring), tensioning said string 821 such that the loop or lasso formedaround the periphery 750 of flared distal end 820 contracts at a ratecontrolled by the retraction, decreasing the diameter of the opening ofthe flared distal end 820 to the desired diameter.

According to some embodiments, the flared distal end may be straight(non-flared) on insertion into a blood vessel, and then flare afterinsertion into the blood vessel. According to some embodiments, theflaring of the flared end is triggered by body temperature, unsheathingfrom within another catheter, or any other mechanism. According to someembodiments, the flared end is retracted (back to non-flared state) bythe lasso mechanism of FIG. 7K, retraction into another catheter,retraction cables, or any other mechanism.

The present invention is a continuation in part of parents teaching amicrocatheter for simultaneous rotation, separation and irrigation forthrombectomy and method which are described herein. The novel featuresof the present disclosure are depicted in FIGS. 18-29.

More particularly, referring to FIG. 18, which discloses lasso channel823. At least one string 821 is wound around reel 822 enters lassochannel 823 by proximal hole 701 and exits catheter 823 via distal hole702. Attached to the rim of distal hole 702 is staff 740 and peripheralfilter ring 750 which forms the proximal end of semi-permeable flaredfilter 760. Said filter 760 is attached to staff 740 such that distaltip 761 of flared filter 760 is proximal to distal tip 741 of staff 740.Staff 740 attaches to lasso channel 823 at attachment point 742. Atleast one string 821, upon exiting lasso channel 823 via end hole 702,extends into a channel around peripheral ring 750 and is attached tofixation point 824. The portion of string 821 in ring 750 is slidable.Fixation point 824 is located on the rim of distal hole 702. Peripheralfilter ring 750 may be rigid or semirigid. String 821 may be a string ora cable, said string or cable 821 may be malleable, rigid, or semirigid.

Now referring to the optional embodiment shown in FIG. 19, the distalend of string 821 is attached to a proximal section of string 821 atattachment point 824 forming a fixed-length lasso. In this embodiment,no fixed-point 824 is required. When string 821 is retracted, the lassodiameter outside end hole 702 decreases, and closes the proximal openingof flared filter 760.

Now referring to an alternate embodiment shown in FIG. 20, peripheralring 750 is disposed with hoops 825 instead of a channel wherein string821 passes through and terminates at fixation point 824.

Now referring to an alternate embodiment shown in FIG. 21A, across-sectional view (line A-A of FIG. 18) of the lasso channel 823.Within said cross-section is disposed a moveable element 713, which ispart of the lasso channel 823 wall. In this embodiment, filter elementsnot mounted to the tip of lasso channel 823 may be deployed.

FIG. 21B presents an alternate embodiment of filter-tipped lasso channel823 which includes moveable elements 713.

Now referring to an alternate embodiment shown in FIG. 22, flared filter769 is depicted in an opposite orientation from the embodiment of filter760 shown in FIG. 18. Said oppositely oriented filter 769 is fixed tothe outside of lasso channel 823 along its length. Rim 750 of filter 769is attached to staff wire 7400 via strut wires 7500. Each strut wire7500 attaches at each end, one end at dispersed points about peripheralrim 750 of rotated filter 769, and the opposite end of each strut wireor string 7500 together at single junction point 7401 on staff wire7400. Staff wire 7400 runs through lasso channel 823 from reel orratcheting mechanism 822 through and out distal hole 702. The rotationof reel or ratcheting mechanism 822 allows either the lengthening orshortening of wire 7400 which in turn contracts or expands the distancebetween strut wires 7500, which allows the opening and closing ofperipheral ring 750 of filter 769.

Now referring to another embodiment shown in FIG. 23, disclosed is theoppositely-oriented flared filter 769 of FIG. 22 without a staff wire7400 or strut wires 7500. In this embodiment, attachment point 7755forms a fixed-length lasso closing mechanism.

Referring now to FIG. 24, disclosed is yet another embodiment shownwherein flared filter 760 opens and closes by additional string 7200passing through side hole 8000 of lasso channel 823. Side hole 8000 islocated at bend 8500. The distal end of said string 7200 is attached tothe proximal end at least one strut string or wires 7500, The distal endof strut string or wires 7500, in turn, attach to rim 750. When string7200 is extended or withdrawn through lasso channel 823, strut strings7500 lengthens or contracts which opens or closes peripheral ring 750.

Now referring to FIG. 25, disclosed is another embodiment having afiltered-tip 9000 affixed at the tip of lasso channel 823 with afixed-loop closing mechanism. In this embodiment, the fixed-loop closingmechanism is embodied by having the distal end of at least one string orwire 7201 fixed to a proximal point on at least one string or wire 7201forming a fixed-loop closing mechanism which operates as follows: whenat least one string 7201 is pulled through the distal end 7001 of innercatheter 7000, such that the distal rim 9100 of filtered-tip 9000closes. Filtered-tip 9000 is usually self-expanding but can beoptionally restrained by the “lasso” element for insertion. In a furtheralternative, said filtered-tip 9000 can be delivered through an outerdelivery catheter, optionally including a “rapid exchange” catheter.Filtered-tip 9000 further includes at least one collapsible ring channel9100 peripherally disposed at the distal end of filtered-tip 9000. Lassochannel 823 in this embodiment further encloses inner catheter 7000which, in turn, contains at least one string 7201. Said at least onestring 7201 further depicting attachment point 9755 forming afixed-length lasso. When at least one string 7201 is extended orwithdrawn through catheter 7000, string 7201 lengthens or contractswhich opens or closes peripheral ring 9100. Said at least one string7201 may be rigid or semirigid.

FIG. 26 discloses the embodiment of FIG. 25, wherein the fixed-loopclosing mechanism is replaced by a drawstring-closing mechanism. Moreparticularly, in the alternate embodiment of filtered-tip 9000 affixedat the tip of lasso channel 823, the distal end of at least one string7201, after passing out of the distal end hole 7777 of catheter 7000,circles through channel 7766 which is located on the distal end offiltered-tip 9000, and returns to a fixation point 7300 located on thetip of catheter 7000. This drawstring mechanism operates by extending orwithdrawing string 7201 which in turn opens or closes channel 7766,which in turn opens and closes filtered-tip 9000.

FIG. 27 discloses the embodiment of FIG. 26, wherein channel 7766 isreplaced by hoops 7765.

FIG. 28 discloses the embodiment of FIG. 26, wherein catheter 7000 isembedded in the wall of lasso channel 823, thus resulting in adrawstring closing mechanism. Catheter segment 7077 is the portion ofembedded catheter 7000 that exits the wall of channel 823 at location7890. Element 7077 located at the proximal section of catheter 7000 iscollapsible.

FIG. 29 discloses the embodiment of FIG. 28, wherein channel 7766 isreplaced by hoops 7765.

The various components of the described invention may comprise one ormore materials. For example, according to some embodiments, thecomponents can comprise one or more of thermoplastics, a thermoset, acomposite or a radiopaque filler.

Thermoplastics include, but are not limited to, nylon, polyethyleneterephthalate (PET), urethane, polyethylene, polyvinyl chloride (PVC)and polyether ether ketone (PEEK).

Thermosets include, but are not limited to, silicone,polytetrafluoroethylene (PTFE) and polyimide.

Composites include, but are not limited to, liquid crystal polymers(LCP). LCPs are partially crystalline aromatic polyesters based onp-hydroxybenzoic acid and related monomers. LCPs are highly orderedstructures when liquid, but the degree of order is less than that of aregular solid crystal. LCPs can be substituted for such materials asceramics, metals, composites and other plastics due to their strength atextreme temperatures and resistance to chemicals, weathering, radiationand heat. Non-limiting examples of LCPs include wholly or partiallyaromatic polyesters or copolyesters such as XYDAR® (Amoco) or VECTRA®(Hoechst Celanese). Other commercial liquid crystal polymers includeSUMIKOSUPER™ and EKONOL™ (Sumitomo Chemical), DuPont HX™ and DuPontZENITE™ (E.I. DuPont de Nemours), RODRUN™ (Unitika) and GRANLAR™(Grandmont).

Non-limiting examples of radiopaque fillers include barium sulfate,bismuth oxychloride, tantalum and the like.

According to some embodiments, the invention comprises component partsmade of material and dimensions having varying stiffness. According tosome embodiments, the invention comprises component parts made ofmaterial and dimensions having the same stiffness. The term “stiffness”as used herein refers to the extent to which an object resistsdeformation in response to an applied force. By way of non-limitingexample, according to some embodiments, the stiffness of the half-loopstructures is less than the rotational stiffness of the central tube.According to some embodiments, the stiffness of the half loop structuresis such that the half loop structures bend upon contact with athrombosis while being rotated within a blood vessel. According to someembodiments, the stiffness of the half loop structures is such that thehalf loop structures do not bend upon contact with a thrombosis whilebeing rotated within a blood vessel. According to some embodiments, thestiffness of the half loop structures is variable; i.e. some half loopstructures have a greater or lesser stiffness compared to other halfloop structures.

According to some embodiments, the microcatheter can extend beyond theopening of the aspiration catheter between 0.1 cm and 100 cm. Accordingto some embodiments, the microcatheter can extend beyond the opening ofthe aspiration catheter by 5 cm. According to some embodiments, themicrocatheter can extend beyond the opening of the aspiration catheterby 10 cm. According to some embodiments, the microcatheter can extendbeyond the opening of the aspiration catheter by 15 cm. According tosome embodiments, the microcatheter can extend beyond the opening of theaspiration catheter by 20 cm. According to some embodiments, themicrocatheter can extend beyond the opening of the aspiration catheterby 25 cm. According to some embodiments, the microcatheter can extendbeyond the opening of the aspiration catheter by 30 cm. According tosome embodiments, the microcatheter can extend beyond the opening of theaspiration catheter by 35 cm. According to some embodiments, themicrocatheter can extend beyond the opening of the aspiration catheterby 40 cm. According to some embodiments, the microcatheter can extendbeyond the opening of the aspiration catheter by 45 cm. According tosome embodiments, the microcatheter can extend beyond the opening of theaspiration catheter by 50 cm. According to some embodiments, themicrocatheter can extend beyond the opening of the aspiration catheterby 60 cm. According to some embodiments, the microcatheter can extendbeyond the opening of the aspiration catheter by 70 cm. According tosome embodiments, the microcatheter can extend beyond the opening of theaspiration catheter by 80 cm. According to some embodiments, themicrocatheter can extend beyond the opening of the aspiration catheterby 90 cm. According to some embodiments, the microcatheter can extendbeyond the opening of the aspiration catheter by 100 cm.

According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of between 5 cmand 500 cm. According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 10 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 20 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 30 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 40 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 50 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 70 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 90 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 100 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 120 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 140 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 160 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 180 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 200 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 250 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 300 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 350 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 400 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 450 cm.According to some embodiments, one or more of the microwire,microcatheter, or aspiration catheter comprises a length of 500 cm.

According to some embodiments, the half loop structures comprise alength (i.e. the distance from the surface to which they are attached tothe farthest part of the half loop from that surface) of 0.1 mm to 5 cm.According to some embodiments, the half loop structures comprise alength of 0.1 mm. According to some embodiments, the half loopstructures comprise a length of 0.5 mm. According to some embodiments,the half loop structures comprise a length of 1 mm. According to someembodiments, the half loop structures comprise a length of 2 mm.According to some embodiments, the half loop structures comprise alength of 4 mm. According to some embodiments, the half loop structurescomprise a length of 6 mm. According to some embodiments, the half loopstructures comprise a length of 8 mm. According to some embodiments, thehalf loop structures comprise a length of 1 cm. According to someembodiments, the half loop structures comprise a length of 2 cm.According to some embodiments, the half loop structures comprise alength of 3 cm. According to some embodiments, the half loop structurescomprise a length of 4 cm. According to some embodiments, the half loopstructures comprise a length of 5 cm.

According to some embodiments, the central wire and/or microcatheter isstraight. According to some embodiments, the central wire and/ormicrocatheter is curved. According to some embodiments, the central wireand/or microcatheter comprises one or more bends of between 5 degreesand 85 degrees before or within the region comprising side holes or halfloop structures. According to some embodiments, the central wire and/ormicrocatheter comprises one or more bends of 5 degrees before or withinthe region comprising side holes or half loop structures. According tosome embodiments, the central wire and/or microcatheter comprises one ormore bends of 15 degrees before or within the region comprising sideholes or half loop structures. According to some embodiments, thecentral wire and/or microcatheter comprises one or more bends of 25degrees before or within the region comprising side holes or half loopstructures. According to some embodiments, the central wire and/ormicrocatheter comprises one or more bends of 35 degrees before or withinthe region comprising side holes or half loop structures. According tosome embodiments, the central wire and/or microcatheter comprises one ormore bends of 45 degrees before or within the region comprising sideholes or half loop structures. According to some embodiments, thecentral wire and/or microcatheter comprises one or more bends of 55degrees before or within the region comprising side holes or half loopstructures. According to some embodiments, the central wire and/ormicrocatheter comprises one or more bends of 65 degrees before or withinthe region comprising side holes or half loop structures. According tosome embodiments, the central wire and/or microcatheter comprises one ormore bends of 75 degrees before or within the region comprising sideholes or half loop structures. According to some embodiments, thecentral wire and/or microcatheter comprises one or more bends of 85degrees before or within the region comprising side holes or half loopstructures.

According to some embodiments, the central wire and/or microcathetercomprises one or more bends before or within the region comprising theside holes or half loop structures such that it is adapted for largevessel application (e.g. pulmonary artery and iliac vein/inferior venacava) so a small device can still effectively sweep along the walls ofthe blood vessel. According to some embodiments, the distal portion ofthe central wire and/or microcatheter comprises a repeating curve orother shape (e.g., sinusoidal shape).

According to some embodiments, a microcatheter or a central wirecomprises a repeating curve or other shape that is adapted to macerate aclot while rotating within and/or beyond the clot. According to someembodiments, a microcatheter or a central wire comprises an irregularshape that is adapted to macerate a clot while rotating within and/orbeyond the clot. According to some embodiments, a microcatheter orcentral wire can have a repeating curve or irregular shape at the distalend. According to some embodiments, a microcatheter or central wire canrotate around the central axis of the blood vessel in which themicrocatheter or central wire is disposed. According to someembodiments, when the microcatheter or central wire are rotated aroundthe central axis of the blood vessel, a repeating curve or irregularshaped portion at the distal end will sweep the interior space of theblood vessel, and break up or macerate a blockage.

According to some embodiments, the described invention can be used in anendovascular procedure in a subject suffering from an arterialthrombosis or embolus. According to some embodiments, the describedinvention can be used in an endovascular procedure in a subjectsuffering from a venous thrombus or embolus. According to someembodiments, the described invention can be used in an endovascularprocedure in a subject suffering from deep vein thrombosis of the leg orarm. According to some embodiments, the described invention can be usedin an endovascular procedure in a subject suffering from myocardialinfarction with thrombus. According to some embodiments, the describedinvention can be used in an endovascular procedure in a subjectsuffering from cerebral venous sinus thrombosis. According to someembodiments, the described invention can be used in an endovascularprocedure in a subject suffering from acute stroke. According to someembodiments, the described invention can be used in an endovascularprocedure comprising mechanical thrombectomy. According to someembodiments, the described invention can be used in an endovascularprocedure comprising proximal endovascular thrombectomy. According tosome embodiments, the described invention can be used in an endovascularprocedure comprising distal endovascular thrombectomy. According to someembodiments, the described invention can be used in an endovascularprocedure comprising percutaneous coronary intervention (PCI). Accordingto some embodiments, the described invention can be used in anendovascular procedure comprising atherectomy. According to someembodiments, the described invention can be used in conjunction withself-expanding stents and retrievable thrombectomy stents. According tosome embodiment, the described invention is adapted to traverse one ormore blood vessels (e.g. vein or artery) of the legs, arms, torso, neck,and head. According to some embodiments, the described invention isadapted to be a universal device capable of traversing any blood vessel(e.g. vein or artery) in the human or animal body.

According to some embodiments, an aspiration catheter 1020 as depictedin FIG. 8 comprises a semipermeable filter 1030 connected to theaspirating end of the catheter. According to some embodiments, thesemipermeable filter 1030 allows blood cells to pass through unimpeded,but captures emboli. According to some embodiments, the semipermeablefilter comprises a flared shape, wherein the distal edge 1060 of thefilter comprises a greater diameter than the remaining portion of thefilter (e.g. the shape of the bell of a trombone). According to someembodiments, the distal edge 1060 of the semi-permeable filter 1030 isable to expand to the diameter of a blood vessel, thereby forcing allblood traversing the blood vessel to pass through the filter.

According to some embodiments, the diameter of the distal edge 1060 ofthe semi-permeable filter comprises a diameter at least 10% greater thanthe diameter of the aspiration catheter 1020. According to someembodiments, the diameter of the distal edge 1060 of the semi-permeablefilter comprises a diameter at least 15% greater than the diameter ofthe aspiration catheter 1020. According to some embodiments, thediameter of the distal edge 1060 of the semi-permeable filter comprisesa diameter at least 20% greater than the diameter of the aspirationcatheter 1020. According to some embodiments, the diameter of the distaledge 1060 of the semi-permeable filter comprises a diameter at least 25%greater than the diameter of the aspiration catheter 1020. According tosome embodiments, the diameter of the distal edge 1060 of thesemi-permeable filter comprises a diameter at least 30% greater than thediameter of the aspiration catheter 1020. According to some embodiments,the diameter of the distal edge 1060 of the semi-permeable filtercomprises a diameter at least 35% greater than the diameter of theaspiration catheter 1020. According to some embodiments, the diameter ofthe distal edge 1060 of the semi-permeable filter comprises a diameterat least 40% greater than the diameter of the aspiration catheter 1020.According to some embodiments, the diameter of the distal edge 1060 ofthe semi-permeable filter comprises a diameter at least 45% greater thanthe diameter of the aspiration catheter 1020. According to someembodiments, the diameter of the distal edge 1060 of the semi-permeablefilter comprises a diameter at least 50% greater than the diameter ofthe aspiration catheter 1020. According to some embodiments, thediameter of the distal edge 1060 of the semi-permeable filter comprisesa diameter at least 55% greater than the diameter of the aspirationcatheter 1020. According to some embodiments, the diameter of the distaledge 1060 of the semi-permeable filter comprises a diameter at least 60%greater than the diameter of the aspiration catheter 1020. According tosome embodiments, the diameter of the distal edge 1060 of thesemi-permeable filter comprises a diameter at least 65% greater than thediameter of the aspiration catheter 1020. According to some embodiments,the diameter of the distal edge 1060 of the semi-permeable filtercomprises a diameter at least 70% greater than the diameter of theaspiration catheter 1020. According to some embodiments, the diameter ofthe distal edge 1060 of the semi-permeable filter comprises a diameterat least 75% greater than the diameter of the aspiration catheter 1020.According to some embodiments, the diameter of the distal edge 1060 ofthe semi-permeable filter comprises a diameter at least 80% greater thanthe diameter of the aspiration catheter 1020. According to someembodiments, the diameter of the distal edge 1060 of the semi-permeablefilter comprises a diameter at least 85% greater than the diameter ofthe aspiration catheter 1020. According to some embodiments, thediameter of the distal edge 1060 of the semi-permeable filter comprisesa diameter at least 90% greater than the diameter of the aspirationcatheter 1020. According to some embodiments, the diameter of the distaledge 1060 of the semi-permeable filter comprises a diameter at least 95%greater than the diameter of the aspiration catheter 1020. According tosome embodiments, the diameter of the distal edge 1060 of thesemi-permeable filter comprises a diameter at least 100% greater thanthe diameter of the aspiration catheter 1020. According to someembodiments, the diameter of the distal edge 1060 of the semi-permeablefilter comprises a diameter at least 200% greater than the diameter ofthe aspiration catheter 1020. According to some embodiments, thediameter of the distal edge 1060 of the semi-permeable filter comprisesa diameter at least 300% greater than the diameter of the aspirationcatheter 1020. According to some embodiments, the diameter of the distaledge 1060 of the semi-permeable filter comprises a diameter at least400% greater than the diameter of the aspiration catheter 1020.According to some embodiments, the diameter of the distal edge 1060 ofthe semi-permeable filter comprises a diameter at least 500% greaterthan the diameter of the aspiration catheter 1020. According to someembodiments, the diameter of the distal edge 1060 of the semi-permeablefilter comprises a diameter at least 600% greater than the diameter ofthe aspiration catheter 1020. According to some embodiments, thediameter of the distal edge 1060 of the semi-permeable filter comprisesa diameter at least 700% greater than the diameter of the aspirationcatheter 1020. According to some embodiments, the diameter of the distaledge 1060 of the semi-permeable filter comprises a diameter at least800% greater than the diameter of the aspiration catheter 1020.According to some embodiments, the diameter of the distal edge 1060 ofthe semi-permeable filter comprises a diameter at least 900% greaterthan the diameter of the aspiration catheter 1020. According to someembodiments, the diameter of the distal edge 1060 of the semi-permeablefilter comprises a diameter at least 1000% greater than the diameter ofthe aspiration catheter 1020.

According to some embodiments, the semi-permeable filter 1030 comprisesa net structure as depicted in FIGS. 11A, 11B, 12A, 12B, and 13 that iseffective to capture emboli that can result from maceration of a bloodclot. According to some embodiments, the semi-permeable filter 1030 iseffective to capture particulates greater than 10 μm in size. Accordingto some embodiments, the semi-permeable filter 1030 is effective tocapture particulates greater than 15 μm in size. According to someembodiments, the semi-permeable filter 1030 is effective to captureparticulates greater than 20 μm in size. According to some embodiments,the semi-permeable filter 1030 is effective to capture particulatesgreater than 30 μm in size. According to some embodiments, thesemi-permeable filter 1030 is effective to capture particulates greaterthan 40 μm in size. According to some embodiments, the semi-permeablefilter 1030 is effective to capture particulates greater than 50 μm insize. According to some embodiments, the semi-permeable filter 1030 iseffective to capture particulates greater than 70 μm in size. Accordingto some embodiments, the semi-permeable filter 1030 is effective tocapture particulates greater than 100 μm in size. According to someembodiments, the semi-permeable filter 1030 is effective to captureparticulates greater than 500 μm in size.

According to some embodiments, as depicted in FIG. 8, the semi-permeablefilter is held in a non-expanded state by rigid wings 1040 connected toa central tube 1050. According to some embodiment, the wings 1040 areformed in the shape of a skirt that defines a space in which thecompressed semi-permeable filter can reside. According to someembodiments, the edge 1070 of the wings 1040 comprises a diameter lessthan the internal diameter of the aspiration catheter 1020. According tosome embodiments, the rigidity of the wings 1040 opposes the expansionof the semipermeable filter 1030 into an expanded shape. According tosome embodiments, the wings 1040 completely surround the semi-permeablefilter 1030. According to some embodiments, the wings 1040 onlypartially surround the semi-permeable filter.

According to some embodiments, the wings 1040 and central tube 1050 canbe pushed in a direction away from the aspiration catheter 1020 andsemi-permeable filter 1030 by an introducer 1010. According to someembodiments, the introducer 1010 surrounds the central tube 1050, andcan move independently along the length of central tube 1050. Accordingto some embodiments, the introducer can push the central tube 1050 andwings 1040 away from the semi-permeable filter such that the expansionof the semi-permeable filter 1030 is no longer constrained by the wings1040. According to some embodiments, the introducer 1010 can be removedfrom the central tube 1050 and aspiration catheter 1020 by withdrawingalong the length of the central tube and aspiration catheter.

According to some embodiments, the outer diameter of the introducer 1010is approximately equal to the inner diameter of the aspiration catheter1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 95% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 90% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 85% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 80% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 75% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 70% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 65% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 60% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 55% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 50% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 45% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 40% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 35% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 30% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 25% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 20% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 15% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 10% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 5% of the inner diameter of the aspirationcatheter 1020. According to some embodiments, the outer diameter of theintroducer 1010 is equal to 1% of the inner diameter of the aspirationcatheter 1020.

According to some embodiments, the wings 1040 and central tube 1050 canbe removed from the blood vessel by withdrawing them through the openingand along the length of the aspiration catheter 1020. According to someembodiments, the edge 1070 of the wings 1040 comprises a diameter lessthan the opening of the aspiration catheter 1020 so that the wings andcentral tube 1050 may be withdrawn through the opening and along thelength of the inside of the aspiration catheter.

With reference to FIG. 9, the central tube is a hypotube 390 thatrotates, macerates and irrigates inside blood vessel 2000 (showncutaway). Hypotube 390 further includes multiple irrigation side holes330, proximal end hole 350 and distal end hole 340. In one embodimenthypotube 390 is sinusoidal.

This embodiment differs from prior art in that the present invention iscapable of discharging liquids from side holes 330. As previously noted,the prior art, as embodied in the ArgonCleaner XT, teaches a distal endhole which dispenses liquid and a cable to macerate clots. Said priorart results in one-sided reduction of clots leading to vessel collapseassisted with creation of a vacuum.

Mechanisms for Retracting the Filter—Magnetic System and Ring SheathSystem

According to some embodiments, as depicted in FIGS. 10A and 10B, thesemi-permeable filter 1030 can be compressed so that the edge 1060 isless than or equal to the diameter of the aspiration catheter 1020.According to some embodiments, the edge 1060 of the semi-permeablefilter 1030 further comprises a magnet component 1080. According to someembodiments, the magnet component is connected to one or more wires1090, which run the length of the aspiration catheter 1020 to a powersource outside of the patient's body. According to some embodiments, themagnetic component 1080 comprises a solenoid, comprising a conductivewire 1090 coiled around a ferromagnetic metal, which can produce amagnetic field to attract one or more magnetic components by passing acurrent through the wire 1090. According to some embodiments, themagnetic component comprises a first magnetic component comprising astraight or curved ferromagnetic metal bar wrapped in an insulatedcopper wire, a second magnetic component comprising a ferromagneticmetal, and a third magnetic component comprising a ferromagnetic metal.According to some embodiments, when current is passed through theinsulated copper wire wrapped around the metal bar, a magnetic field isproduced around the first magnetic component, which attracts the secondmagnetic component and third magnetic component. According to someembodiments, the force of magnetic attraction between the magneticcomponents is strong enough to overcome the intrinsic resilience of thesemi-permeable filter 1030 to maintain a flared shape, resulting in acollapse of the filter 1030.

According to some embodiments, the semi-permeable filter comprises aplurality of magnetic components comprising a conductive wire coiledaround a ferromagnetic metal. According to some embodiments, thesemi-permeable filter comprises a plurality of magnetic componentscomprising a ferromagnetic metal without a coiled wire. According tosome embodiments, the semi-permeable filter comprises a plurality ofmagnetic components arranged in a manner adapted to collapse thesemi-permeable filter such that no part of the semipermeable filtercomprises a diameter greater than the diameter of the aspirationcatheter.

According to some embodiments, the semi-permeable membrane comprisessolenoids with magnetic poles approximately parallel to the surface ofthe semi-permeable membrane. According to some embodiments, thesemi-permeable membrane comprises a first magnetic component comprisinga solenoid arranged opposite to a second solenoid, wherein a current ispassed through the coiled wire of each solenoid, and the resultingmagnetic fields have opposing poles across the semi permeable membrane.For example, for a semi-permeable membrane comprising two solenoids, thesolenoids are arranged so that the north pole of the first solenoid isopposite to the south pole of the second solenoid, and the south pole ofthe first solenoid is opposite to the north pole of the second solenoid.Thus, in this specific example, the opposite poles will attract oneanother across the distance of the semi-permeable membrane, thuscollapsing the semi-permeable membrane.

According some embodiments, the solenoids are arranged so that theopposing poles of the solenoid are perpendicular to the semi-permeablemembrane. According to some embodiments, the semi-permeable membranecomprises a first magnetic component comprising a solenoid perpendicularto the semi-permeable membrane arranged opposite to a second solenoidperpendicular to the semi-permeable membrane. For example, the northpole of the first solenoid is pointed toward the inner space defined bythe semi-permeable membrane, and the south pole of the second solenoidis pointed toward the inner space defined by the semi-permeablemembrane. Thus, in this specific example, the opposite poles will beattracted to one another across the distance of the semi-permeablemembrane, thus collapsing the semi-permeable membrane.

According to some embodiments, the semi-permeable membrane comprisesmagnetic components at varying distances from the aspiration catheter.For example, some embodiments may comprise a first pair of magneticcomponents in the distal edge of the semi-permeable membrane, a secondpair of magnetic components approximately equidistance from the distaledge and the proximal edge of the semi-permeable membrane, and a thirdpair of magnetic components approximately equidistance from the secondpair of magnetic components and the proximal edge of the semi-permeablemembrane.

According to some embodiments, the semi-permeable membrane comprisesmagnetic components arranged in a manner adapted to fold thesemi-permeable membrane into a shape where no part of the semi-permeablemembrane falls outside the diameter of the aspiration catheter.According to some embodiments, the semi-permeable membrane comprisingthe magnetic components and aspiration catheter is introduced into theblood vessel of a patient with the magnetic fields of the magneticcomponent holding the semipermeable membrane in a folded position, andupon arriving at the desired position in the blood vessel the magneticfield is turned off and the intrinsic resilience of the semi-permeablemembrane unfolds the semi-permeable membrane into a flared shape.According to some embodiments, the semi-permeable membrane is re-foldedby turning on the magnetic field of the magnetic components prior toremoving the aspiration catheter and semi-permeable membrane from theblood vessel.

According to some embodiments (FIGS. 11A, 11B), a semi-permeablemembrane can be expanded to a flared shape or collapsed into a foldedshape via movement of a rigid ring 1090 structure positioned outside ofthe semi-permeable filter 1030. According to some embodiments, thesemi-permeable filter is connected to the aspiration catheter 1020 belowthe rigid ring 1090. According to some embodiments, the rigid ring 1090can be pushed out of the end of the aspiration catheter, forcing thesemi-permeable filter 1030 to collapse. According to some embodiments,the rigid ring 1090 can be connected to a stiff wire 1100. According tosome embodiments, the stiff wire can push the rigid ring 1090 out of theaspiration catheter to surround and collapse the semi-permeable filter1030.

According to some embodiments, as depicted in FIGS. 11A, 11B, 13A and13B, a semi-permeable membrane can be expanded or collapsed into afolded shape via movement of a rigid ring structure 1091 that extendsfrom the aspiration catheter. According to some embodiments, the filter1030 is attached to the inside of the aspirating end of the aspirationcatheter 1020 and the rigid ring structure 1091 abuts the aspirating endof the aspirating catheter, acting as an extension of the aspiratingcatheter. According to some embodiments, the rigid ring structure can beadvanced over the filter 1030 by being pushed by one or more stiff wires1100. According to some embodiments, the rigid ring 1091 does not reducethe cross-sectional area through which aspiration occurs.

According to some embodiments, as depicted in FIGS. 12A and 12B, theaspiration catheter 1020 can be housed within an outer catheter 1110.According to some embodiments, the outer diameter of the aspirationcatheter 1020 can be approximately equal to the inner diameter of theouter catheter 1110. According to some embodiments, the inner aspirationcatheter 1020 can move independently within the outer catheter 1110.According to some embodiments, the outer catheter 1110 is rigid enoughsuch that the semi-permeable filter is forced to collapse when the inneraspiration catheter 1020 is withdrawn inside the outer catheter 1110.

According to some embodiments of the present invention, using thefilter-tip aspiration catheter device, the vein or artery is accesseddownstream from the clot, and the filter-tip aspiration catheter isdeployed downstream from the clot. This is usually easy to accomplish inmost venous thrombi and emboli. This is usually not possible forarterial emboli in the brain. But in some arm and leg cases it can be. Anon-limiting example is an axillary artery embolus/thrombus, where aperson of ordinary skill can get access proximal to the clot fromfemoral insertion, and/or a person of ordinary skill in the art canaccess distally (downstream) via a brachial artery or radial arteryaccess as well.

According to one aspect of the present invention, one or moreembodiments of the apparatuses shown and described are used for one ormore of irrigation, maceration, and aspiration of a blockage in apatient's blood vessel.

Method 1: Irrigation and Maceration Only

For example, according to some embodiments, a method of irrigating andmacerating a blockage of a blood vessel comprises introducing arotating, irrigating catheter into the blood vessel of a patient,advancing the catheter to the site of a blockage, penetrating theblockage with the catheter, macerating the blockage by rotating thecatheter and irrigating within and beyond the blockage with thecatheter. According to some embodiments, the maceration and irrigationcan be constant. According to some embodiments, the maceration isconstant while the irrigation is intermittent. According to someembodiments the maceration is intermittent while the irrigation isconstant. According to some embodiments, the maceration and irrigationare both intermittent. According to some embodiments, the maceration andirrigation occur simultaneously. According to some embodiments, themaceration and irrigation occur asynchronously. Irrigation is sufficientto keep the vessels from collapsing.

Method 2: Only Irrigation and Aspiration

According to some embodiments, a method of removing a blockage in ablood vessel comprises introducing an irrigating catheter and anaspiration catheter into the blood vessel of a patient, advancing theirrigating and aspirating catheters to the site of a blockage,penetrating the blockage with the irrigating catheter, aspirating theblockage, and irrigating the blockage. According to some embodiments,the blockage comprises cells, cell debris, emboli, or other material, ora combination thereof. According to some embodiments, the aspiration isconstant and the irrigation is constant. According to some embodiments,the aspiration is intermittent and the irrigation is intermittent.According to some embodiments, the aspiration is intermittent and theirrigation is constant. According to some embodiments, the aspiration isconstant and the irrigation is intermittent. According to someembodiments, the aspiration and irrigation occurs simultaneously.According to some embodiments, the aspiration and irrigation occursasynchronously. The present invention uses irrigation and aspiration toreverse blood flow while maintaining sufficient vascular volume andpressure to prevent the vessel from collapsing. This use of the presentinvention is independent of maceration.

Method 3: Maceration, Irrigation, and Aspiration

According to some embodiments, a method of removing a blockage in ablood vessel comprises introducing a macerating, irrigating catheter andan aspiration catheter into the blood vessel of the patient, advancingthe irrigating and aspirating catheters to the site of a blockage,penetrating the blockage with the macerating, irrigating catheter,macerating the blockage, irrigating the blockage, and aspirating theblockage. According to some embodiments, the blockage comprises cells,cell debris, emboli, or other material, or a combination thereof.According to some embodiments, the aspiration, maceration, andirrigation are constant. According to some embodiments, the aspiration,maceration, and irrigation are intermittent. According to someembodiments, the aspiration is constant while the maceration andirrigation are intermittent. According to some embodiments, theaspiration and the maceration are constant while the irrigation isintermittent. According to some embodiments, the aspiration andirrigation is constant while the maceration is intermittent. Accordingto some embodiments, the irrigation is constant while the maceration andaspiration are intermittent. According to some embodiments, two or moreof the aspiration, irrigation, and maceration occurs simultaneously.According to some embodiments, two or more of the aspiration,irrigation, and maceration occurs asynchronously. The present inventioncan be used with or without a balloon (said balloon is any intentionallyemployed blood-flow blocking device). Said blood-flow blocking devicemay partially or completely block blood flow. The objective of usingsaid blood-flow blocking device is to assist the present invention inreversing blood flow.

Method 5: Combining any Combination of Methods 1, 2, and 3, with a ClotRetrieval Device, a Non-Limiting Example of which is a Retrievable StentSuch a Solitaire (Medtronic) or Trevo (Stryker) Device.

According to some embodiments, a method of removing a blockage in ablood vessel comprises introducing a first device to the site of theblockage to break up the blockage, and introducing a second device at asite away from site of the blockage to capture emboli resulting frombreaking up the blockage. According to some embodiments, the blockagecomprises cells, cell debris, emboli, or other material, or acombination thereof. According to some embodiments, fragments of theblockage that travel in the direction of blood flow can be collected bya semi-permeable filter away from the site of the blockage. According tosome embodiments, the emboli can be removed via aspiration at the siteof the blockage, via an aspiration catheter with an embedded filterextending from its end, with or without additional irrigation and/ormaceration elements at the site of aspiration. Aspiration can be appliedto clear filters when debris builds up on said filters.

According to some optional embodiments of the present invention, anintravenous ultrasound (IVUS) is deployed to monitor blood flow ratethrough said filter. The purpose of inserting an intravenous ultrasound(IVUS) is to monitor blood flow rate through said filter clear so thatin the event a blood clot build-up occurs on the surface of said filterand said blood clot build up slows blood flow by more than eightypercent (80%), then action is taken to remove said blood clot build up.Said removal is typically executed by using an aspirator.

The sinusoidal, hypotube device of the current invention (such asdepicted in FIG. 9) uses an eggbeater-like effect to macerate whilesimultaneously irrigating. The present invention is distinct from theprior art wherein a sinusoidal cable is used but cannot irrigate intoand beyond the clot. The sinusoidal microtube of the present inventioncan vary enormously from a diameter of about 100 mm (four inches) downto approximately 0.1 mm. Referring now to FIG. 14, the present inventioncan be used in conjunction with balloons. Said balloon is mounted toaspiration catheter designed for use at the face of an arterialthrombus, in order to occlude a vessel and facilitate blood-flowreversal via aspiration and simultaneous distal irrigation. The presentinvention also teaches the use of vibrational wire, balloon andaspirator element with or without filters.

Referring to FIG. 15, the simultaneous aspects of the current inventionmay be used in conjunction with the introduction of a secondendovascular device, a filter-tipped aspiration catheter 1500 includingat least one filter 1510 disposed at the distal tip of device 1500.Filter 1510 may optionally comprise a polyurethane membrane with pores,polyester, or other fabric or polymer, further supported by metal orother rigid wires, optionally nytinol. The pore size is 1 μm-250 μm, or0.1 μm-5 mm (different unit intentional).

As depicted in FIG. 15, the rotating irrigation macerating catheter 300is introduced via femoral vein sheath 1530 to the site of iliac clot1570. Said aspiration catheter 1500 is introduced via the jugular vein1580 through the heart 1550 from the opposite direction of blood flow toa position in the inferior vena cava (IVC) 1520 beyond the heart tocatch emboli in deployed filter 1510. The perimeter of deployed filter1510 is proximal to and within the IVC 1520. Blood flows in thedirection of the heart 1550, into filter 1510 potentially carryingparticulate matter freed up by the simultaneous irrigation into andmaceration of the clot. Filter 1510 captures smaller particulate matterthan wire structures used in the prior art, more effectively protectingthe heart 1550 and other organs from the effect of small and mediumsized emboli. Its use also eliminates the significant risks of deployingand removing said wire filter sometimes used in the prior art.

In an alternative embodiment shown in FIG. 16, said aspiration catheter1500 may be introduced via the descending aorta 1680. Said catheter 1500has at least one bend. In FIG. 16, a first bend 1700 and a second bend1701 are illustrated. All optional bends are positioned between filter1510 and the terminus of catheter 1500 outside the body. In thepreferred embodiment, said first bend 1700 occurs proximal to the leftsubclavian artery 1900, but not further than a line defined by the highpoint of aortic arch 2000 and the most proximal opening of the leftcarotid artery 2100. Said second bend 1701 occurs after the line definedby the uppermost point 2000 of the aortic arch and the most proximalopening of the left common carotid artery 2001, and proximal to theinnominate artery 1910. In the preferred embodiment, filter 1510 isdisposed within the ascending aorta 1690. In an optional embodiment,aspiration catheter 1500 is sheathed in outer sheath 1531 for afilter-tip aspiration catheter.

The dimensions of the present invention are as follows: the length ofdevice 1500 is approximately 0.5-160 cm; the diameter of catheter 1500is approximately 0.1 mm-25 mm, and the diameter of the at least onefilter 1510 is approximately 0.1 mm-100 mm. In the preferred embodimentof the present invention filter 1510 is self-expanding. In analternative embodiment, filter 1510 is expanded as a result of a balloon(not shown) expanding proximal to at least one filter 1510.

In an optional embodiment of the present invention, said at least onefilter 1510 may also optionally comprise hydrogel (not shown) disposedupon the peripheral edges 1511 of said filter(s) 1510. In other optionalembodiment, surfaces of the present invention likely to contact a vesselwall when deployed, such as first bend 1700 in FIG. 16, will also have acoating of hydrogel. The deployment of hydrogel as detailed above isintended to improve wall adherence such as at the site of bend 1700,and/or prevent “endoleaks” of unfiltered blood between filter 1510 and avessel wall (as described in claims 10 and 17 of U.S. Pat. No. 9,775,730B1 [Walzman]).

For example, one example of how the device of the present invention maybe used during a heart valve-replacement procedure is as follows. Themethod includes the steps of delivering the present invention via afemoral artery (not shown), over aortic arch 2000, so that filter 1510and catheter tip is facing aortic valve 3000 within the ascending aorta1690—between the heart (aortic valve 3000) and the innominate artery1910.

The next steps of the method include deployment of said at least onefilter 1510, by delivering a replacement valve (not shown) into aorticvalve 3000 and deploying said valve 300, through the “filter-tip guidecatheter”—with filter 1510 capturing all emboli and protecting all threeof the “Great Vessels” (the innominate artery 1910, left common carotidartery 2100, and left subclavian artery 1900, and their distalcirculations), and the entire arterial supply to the body, from embolithat can be displaced during the procedure. Existing prior art such asClaret Medical's Sentinel® Cerebral Protection System, protects only twoof the Great Vessels, omitting the left subclavian 1900. After deployingsaid replacement valve, the delivery system is removed. The filter-tipaspiration catheter 1500 can then optionally be aspirated. Thefilter-tip 1510 is then resheathed. All catheters and sheaths are thenremoved. Hemostasis is achieved by the practitioner's method of choice(using standard techniques).

In an alternative embodiment shown in FIG. 17, said aspiration catheter1500 may be introduced via the descending aorta 1680. Said catheter 1500has at least one bend. In FIG. 17, a first bend 1700 and a second bend1701 are illustrated. All optional bends are positioned between filter1510 and the terminus of catheter 1500 outside the body. In thepreferred embodiment, said first bend 1700 occurs proximal to the leftsubclavian artery 1900, but not further than a line defined by the highpoint of aortic arch 2000 and the most proximal opening of the leftcarotid artery 2100. Said second bend 1701 occurs after the line definedby the uppermost point 2000 of the aortic arch and the most proximalopening of the left common carotid artery 2001, and proximal to theinnominate artery 1910. In the preferred embodiment, filter 1510 isdisposed within the ascending aorta 1690. In an optional embodiment,aspiration catheter 1500. It should be noted that this embodimentdiffers from the embodiment of FIG. 16 in that it lacks outer sheath1531.

An endovascular device for protecting the outflow through the ascendingaorta by capturing emboli is capable of protecting more than the threegreat heart vessels simultaneously. In the preferred embodiment, thepresent invention incorporates an external sheath comprising a proximalend, a wall that comprises a circumference and that spans the proximalend to a distal end, wherein the wall of the catheter defines a luminalspace, a first opening at the proximal end of the catheter, and a secondopening at the distal end of the catheter. Said sheath is capable ofboth designed to allow smooth passage of surgical instruments as well asfor positioning of said instruments.

The present invention also includes an external termination device suchas a Luer Lock, diaphragm, valve among other device which were previousdisclosed in the specification. Said device is attached to the proximalend of said external sheath. Such a device may also be attached to theproximal end of said inner catheter.

It should be noted that the present invention's an inner cathetercomprising a proximal end, a wall that comprises a circumference andthat spans the proximal end to a distal end, wherein the wall of thecatheter defines a luminal space, a first opening at the proximal end ofthe catheter, and a second opening at the distal end of the catheter.Said catheter is made of a range of polymers are used for theconstruction of catheters, including silicone rubber, nylon,polyurethane, polyethylene terephthalate (PET), latex, and thermoplasticelastomers.

The present invention includes at least one flared, semi-permeablefilter adapted to allow passage of blood cells and serum and to captureemboli, said at least one semi-permeable filter circumferentiallyattached to the distal end of said catheter. Said flared filter iscollapsible to accommodate delivery into an appropriate position in theascending aorta, wherein the diameter of said filter, when expanded, issmallest at its proximal attachment to the tip of said inner catheterand larger at its distal segment, wherein when fully expanded the distalsegment of said filter conforms to the walls of the ascending aorta, sothat blood flowing through the ascending aorta travels through saidfilter.

It should also be noted that the present invention's inner catheter hasan outer circumferential diameter that is not more than the innerdiameter of said outer sheath; and the filter disposed on the distal endof said inner catheter is removably attached and deliverable throughsaid external sheath, while remaining attached to said inner catheter.Additionally, the present invention is capable of joining additionaldevices can be delivered through said filter into the portion of theascending aorta closet to the heart, the aortic valve, the heart, and/orcardiac vessels without displacing any portion of said filter.

The present invention has several additional embodiments including onewhich is detachably secured to an external aspiration device at itsexternal termination device, to further facilitate removal of filtereddebris. Other include embodiment with at least 1 bend and yet anotherwith at least 2 bends.

The present intention also uses a filter which is self-expanding uponrelease from an external constraint. Said flexible filter comprises aflexible stent having a plurality of flexible wire segments attachedacross the ends of the stent. The filter is resiliently compressible fors insertion into a vessel and expands against the passageway uponplacement therein. The filter includes different levels of filtration.This filter further comprises shape-memory polymers that cause it toexpand over a set amount of time after introduction into the body.

Additionally, in a separate embodiment the filter expands in response toan additional stimulus. One such nonlimiting example is via a balloonexpansion.

The present invention has additional capabilities, such as acting as aconduit for delivery of a cardiac valve device, acting as a conduit fordelivery of a cardiac ablation device and acting as a conduit fordelivery of a balloon.

The present invention also discloses various optional filter elements.These include: at least one filter comprises a membrane with pores;pores are differentially sized; said pores are less than 200 μM in size;at least one filter is supported by rigid wires; at least one filter issupported by semirigid wires; at least one filter is further supportedby at least 1 rigid wire comprising at least 1 ring; at least one filteris further supported by at least 1 semirigid wire comprising at least 1ring.

All of said filter wherein said wires may use nitinol. They may alsohave disposed upon the peripheral edges of said at least one filter.

In a separate embodiment of the present invention the device is composedof a catheter comprising a proximal end, a wall that comprises acircumference and that spans the proximal end to a distal end, whereinthe wall of the catheter defines a luminal space, a first opening at theproximal end of the catheter, and a second opening at the distal end ofthe catheter; an external termination device (such as Luer Lock,diaphragm, valve—define in spec) attached to the proximal end of saidcatheter; at least one flared, semi-permeable filter adapted to allowpassage of blood cells and serum and to capture emboli, said at leastone semi-permeable filter circumferentially attached to the distal endof said catheter, wherein said flared filter is collapsible toaccommodate delivery into an appropriate position in the ascendingaorta, and wherein the diameter of said filter, when expanded, issmallest at its proximal attachment to the tip of said catheter andlarger at its distal segment, wherein when fully expanded the distalsegment of said filter conforms to the walls of the ascending aorta, sothat blood flowing through the ascending aorta travels through saidfilter; and wherein additional devices can be delivered through saidfilter into the portion of the ascending aorta closet to the heart, theaortic valve, the heart, and/or cardiac vessels without displacing anyportion of said filter

This embodiment has many of the elements of the prior embodiment such asthe fact that it is detachably secured to an external aspiration deviceat its external termination device, to further facilitate removal offiltered debris; may have either at least one (1) bend in said catheteror at least two (2) bends in said catheter; it is self-expanding uponrelease from an external constraint and may be comprised of shape-memorypolymers that cause it to expand over a set amount of time afterintroduction into the body.

More specifically, the present invention discloses that theself-expanding devices can only expand when they are released from “all”constraints. Thus, the present invention is self-expanding upon releasefrom all constraints. Such constraints may include, but are not limitedto, an external sheath covering said filter, internal hooks, and/or ashortened circumferential string. Additionally, and/or alternatively,the filter(s) may be comprised of shape-memory polymers that cause it toexpand upon the application of an additional stimulus, provided thereare no physical constraints to expansion.

The present invention discloses two types of devices which are capableof opening and closing the lasso, which may be known as a rewindingmechanism. They are a ratchet and a reel. A ratchet mechanism the justgrabs and pulls the string along a straight line is more likely than aspinning “reel” (similar to the mechanical detachment mechanism ofPenumbra coils and EV3 coils, as well as (perhaps more-so) similar tothe shortening mechanism of the Rapid Medical Comaneci and Tigertrieverdevices (https://www.rapid-medical.com/comaneci).

The present invention also discloses that “internal” constraints (i.e.constraints which are built into the present invention) such as hookslocated inside of the present invention. The function of said internalconstraints are the same as said external constraints (i.e. to constrainshape change).

The present invention may be used in the following manner comprising thesteps of:

-   -   (a) inserting said external sheath of said device via a femoral        artery,    -   (b) passing distal end of said external sheath over the aortic        arch over a wire and/or an additional catheter, under        fluoroscopic guidance,    -   (c) positioning said distal end of said external sheath into the        ascending aorta    -   (d) removing said additional delivery wire and/or catheter    -   (e) delivering said filter-tipped inner catheter through said        external sheath, optionally over an additional catheter and/or        wire;    -   (f) positioning the distal segment of said filter so that the        end of said filter extends to the end of said external sheath    -   (g) holding said inner catheter steady while said external        sheath is partially withdrawn by the length of said filter,        under fluoroscopic guidance, thereby exposing said filter within        the ascending aorta, thus prompting said (self-expanding        version) filter to expand to conform at its outer segment to the        inner walls of the ascending aorta;    -   (h) delivering an aortic valve device across the aortic valve,        optionally over a wire, via a delivery device detachably        attached to said aortic valve    -   (i) deploying and detaching said aortic valve device;    -   (j) removing said aortic valve delivery device;    -   (k) optionally applying aspiration to said proximal end of the        lumen of said filter-tip inner catheter    -   (l) advancing said external sheath while holding still said        inner catheter, optionally with aspiration still applied, until        the entire filter collapses into said external sheath    -   (m) withdrawing said entire device from the aorta, optionally        with aspiration still applied, and removing it from the body;        and    -   (n) obtaining femoral hemostasis.

The present invention discloses three additional features for thepresent invention. These include (a) an outer sheath, (b) at least onecurve in the catheter, and (c) at least one detachable aspirator.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range is encompassed within the invention. The upper and lowerlimits of these smaller ranges which may independently be included inthe smaller ranges is also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either bothof those included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the described invention, exemplarymethods and materials have been described. All publications mentionedherein are incorporated herein by reference to disclose and describedthe methods and/or materials in connection with which the publicationsare cited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “and”, and “the” include plural references unlessthe context clearly dictates otherwise.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application and eachis incorporated by reference in its entirety. Nothing herein is to beconstrued as an admission that the described invention is not entitledto antedate such publication by virtue of prior invention. Further, thedates of publication provided may be different from the actualpublication dates which may need to be independently confirmed.

While the described invention has been described with reference to thespecific embodiments thereof it should be understood by those skilled inthe art that various changes may be made and equivalents may besubstituted without departing from the true spirit and scope of theinvention. In addition, many modifications may be made to adopt aparticular situation, material, composition of matter, process, processstep or steps, to the objective spirit and scope of the describedinvention. All such modifications are intended to be within the scope ofthe claims appended hereto.

1-30. (canceled)
 31. An endovascular system comprising: an endovasculardevice configured for insertion into a patient, the endovascular devicecomprising: an outer tubular member having proximal and distal ends; aninner tubular member positioned within the outer tubular member; and afilter element supported by a distal end of the inner tubular member andmovable between a collapsed configuration, in which the filter elementis configured for insertion into a patient's vessel, and an expandedconfiguration, in which the filter element extends distally beyond theouter tubular member and flares outwardly to capture emboli whilepermitting blood cells and serum to pass through the filter element tothereby protect tissue supplied by blood travelling therethrough. 32.The endovascular device of claim 31, wherein the endovascular device issteerable.
 33. The endovascular system of claim 31, wherein theendovascular device is configured to receive a supplemental medicaldevice such that the supplemental medical device is advanceable into thepatient through the filter element.
 34. The endovascular system of claim31, wherein the endovascular device is configured to receive areplacement valve such that the replacement valve is advanceable intothe patient through the endovascular device.
 35. The endovascular systemof claim 31, wherein when the filter element is configured to contact awall of the patient's ascending aorta upon expansion to protect bloodflow to the patient's Innominate artery, the patient's left commoncarotid artery, the patient's left Subclavian artery, and tissueslocated distally thereof from embolic injury.
 36. The endovascularsystem of claim 31, wherein the outer tubular member and the innertubular member are configured for relative longitudinal movement and thefilter element is directly and circumferentially attached to the distalend of the inner tubular member such that relative longitudinal movementbetween the outer tubular member and the inner tubular member causesreconfiguration of the filter element between the collapsedconfiguration and the expanded configuration.
 37. The endovascularsystem of claim 36, wherein the outer tubular member defines an internalspace configured to receive and constrain the filter element such thatthe filter element is collapsed when contained within the internalspace, the filter element being configured for self-expansion uponexposure from the internal space.
 38. The endovascular system of claim36, wherein the endovascular device includes an engagement structureconfigured to engage and constrain the filter element to move the filterelement from the expanded configuration into the collapsedconfiguration.
 39. The endovascular system of claim 31, furthercomprising an outer delivery catheter configured to receive theendovascular device to facilitate introduction of the endovasculardevice into a blood vessel.
 40. The endovascular system of claim 39,further comprising a guide member configured for insertion through theouter delivery catheter and through the endovascular device such thatthe outer delivery catheter and the endovascular device are guidedthrough the patient's vasculature over the guide member, the guidemember being configured as a guide wire or as a guide catheter.
 41. Anendovascular system comprising: an endovascular device configured toprotect tissue from emboli during an endovascular procedure, theendovascular device comprising: an inner tubular member; and a filterelement directly and circumferentially attached to a distal end of theinner tubular member such that the filter element extends distally andflares out beyond the inner tubular member, wherein the inner tubularmember and the filter element are configured to receive a supplementalmedical device such that the supplemental medical device is insertableinto a patient through the inner tubular member and the filter element.42. The endovascular system of claim 41, wherein the endovascular devicefurther includes an outer tubular member configured to receive the innertubular member and the filter element so as to allow for relativelongitudinal movement therebetween to collapse and expand the filterelement and facilitate capture of emboli, the filter element expandingautomatically when constraint provided by the outer tubular member isremoved.
 43. The endovascular system of claim 42, wherein the filterelement is semi-permeable so as to allow blood cells and serum to passtherethrough during the capture of emboli.
 44. The endovascular systemof claim 41, wherein the filter element is configured for insertion intothe patient's ascending aorta to filter flow downstream toward thepatient's descending aorta.
 45. The endovascular system of claim 41,further comprising the supplemental medical device, wherein thesupplemental medical device is configured as a replacement heart valveor as a thrombectomy device configured to treat an endovascularblockage.
 46. The endovascular system of claim 41, wherein theendovascular device is steerable.
 47. The endovascular system of claim41, further comprising an aspiration device configured for removableconnection to a proximal end of the inner tubular member.
 48. A methodof filtering emboli to protect against embolic injury duringendovascular treatment of a vessel, the method comprising: inserting anendovascular device downstream of a blockage in the vessel; and causingrelative movement between an outer tubular member and an inner tubularmember of the endovascular device to expose and expand a filter elementdirectly attached to a distal end of the inner tubular member tofacilitate filtration of emboli while permitting blood cells and serumto pass through the filter element.
 49. The method of claim 48, whereinthe method includes protecting three great vessels of a patient's aorticarch and outflow to the patient's aorta during the treatment.
 50. Themethod of claim 48, wherein causing relative movement between the outertubular member and the inner tubular member exposes the filter elementfrom an internal space defined by the outer tubular member such that aflared distal end of the filter element contacts an inner wall of thepatient's aorta.
 51. The method of claim 48, further comprisinginserting a supplemental medical device through the endovascular device.52. The method of claim 51, wherein inserting the supplemental medicaldevice includes inserting a replacement heart valve or inserting a valvedevice.
 53. The method of claim 48, further comprising: advancing atreatment device into the vessel; and treating the blockage using thetreatment device.
 54. The method of claim 48, wherein advancing thetreatment device into the vessel includes advancing the treatment deviceinto the vessel through the inner tubular member and the filter element.